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PubMed1983

Effect of age and environmental factors on insulin release from the perfused pancreas of the rat.

In this study we examined the effect of age and various age-related environmental factors on maximal glucose-stimulated insulin release by the intact perfused pancreas. Male Sprague-Dawley rats were maintained from 40 d to 12 mo of age on standard chow, or on a sucrose-rich or calorie-restricted diet. At 12 mo, studies were carried out on the isolated pancreas of each animal to determine maximal (300 mg/ml) glucose-stimulated insulin secretion. After these studies were completed, each pancreas was perfused with formalin fixative and processed for morphometric estimation of the mass of the endocrine pancreas. Data from these older animals were compared with data from 2-mo-old control rats. The results indicate that maximal glucose-stimulated insulin secretion per unit endocrine pancreas was markedly reduced in all three groups of 12-mo-old rats, and was only 25-33% of that of 2-mo-old rats. Thus, aging led to a decline in insulin secretion per beta cell that was not modifiable by environmental manipulation. On the other hand, environmental factors can influence the development of endocrine tissue within the pancreas, and in so doing, modify total pancreatic insulin secretion. The mass of the endocrine pancreas of 12-mo-old rats fed either sucrose or chow was between three and four times that of 2-mo-old control rats, and these older rats were able to maximally secrete as much insulin per total pancreas as the young rats. In contrast, the endocrine cell mass of the calorie-restricted rats had not enlarged to this extent, and the maximally stimulated perfused pancreas from these rats secreted less insulin. These data suggest that the aging animal, challenged in vivo to secrete insulin, can overcome the loss of the beta cell response by expanding its pancreatic pool of beta cells. Although this compensation is successful in the 12-mo-old, obese, middle-aged rat, it is not yet clear what effect further aging would have on these events.

Aging↗
PubMed1976

Thyroid function and insulin secretion from the perfused pancreas in the rat.

The influence of thyroid function on the kinetics of glucose-induced insulin secretion from the isolated perfused rat pancreas has been studied. L-Thyroxine (L-T4) administration did not modify the immediate insulin secretory response of the perfused pancreas to glucose. L-Triiodothyronine (L-T3) treatment as well as propylthiouracil (PTU) treatment decreased the immediate insulin secretory response of the pancreas slightly. Only thyroidectomy (Tx) reduced the immediate secretory response of the pancreas significantly. L-T4 and L-T3 treatment inhibited the late phase of glucose-induced insulin secretion from the isolated perfused rat pancreas, whereas TX and PTU treatment resulted in increased insulin secretion. D-Thyroxine (D-T4) did not affect glucose-induced insulin release from the pancreas. Concomitantly, several parameters indicative of thyroid function were determined in these animals. When changes in body weight, rectal temperature, plasma glucose, plasma cholesterol, and plasma butanol-extractable iodine (BEI) in these rats were compared with the insulin secretory responses, it was evident that experimental hyperthyroidism results in decreased insulin release, whereas experimental hypothyroidism induces increased insulin secretion from the pancreas. The transitions from hypothyroid to euthyroid to hyperthyroid states are accompanied by a steady decrease in glucose-induced insulin release from the rat pancreas. Inhibition of glucose-induced insulin secretion from the pancreas is therefore a specific effect of thyroid hormones.

Animals↗
PubMed1995

Developmental biology of the pancreas.

The pancreas is an organ containing two distinct populations of cells, the exocrine cells that secrete enzymes into the digestive tract, and the endocrine cells that secrete hormones into the bloodstream. It arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. Mammals, birds, reptiles and amphibians have a pancreas with similar histology and mode of development, while in some fish, the islet cells are segregated as Brockmann bodies. Invertebrates do not have a pancreas, but comparable endocrine cells may be found in the gut or the brain. The early pancreatic bud shows uniform expression of the homeobox gene IPF-1 (also known as IDX-1, STF-1 or PDX), which when mutated to inactivity leads to total absence of the organ. The occurrence of heterotopic pancreas in the embryo, and also the metaplasias that can be displayed by a regenerating pancreas in the adult, both suggest that only a few gene products distinguish the pancreatic cell state from that of the surrounding tissues of duodenum, gall bladder and liver. In the developing pancreatic buds, the endocrine cells start to differentiate before the exocrine cells, and co-expression of different hormones by the same cell is often observed at early stages. Although pancreatic endocrine cells produce many gene products also characteristic of neurons, evidence from in vitro cultures and from quailchick grafts shows that they are of endogenous and not of neural crest origin. Observational studies suggest strongly that both endocrine and exocrine cells arise from the same endodermal rudiment. Development of the pancreas in embryonic life requires a trophic stimulus from the associated mesenchyme. In postnatal life, all cell types in the pancreas continue to grow. Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration. Surgical removal of parts of the pancreas is followed by moderate but incomplete regeneration of both acini and islets. Poisoning with alloxan or streptozotocin can lead to permanent depletion of beta cells. Although the cell kinetics of the pancreas are not understood, it seems likely that there is a continuous slow turnover of cells, fed from a stem cells population in the ducts, and that the controls on the production rate of each cell type are local rather than systemic.

Animals↗
PubMed1998

Acute terminal pancreatitis occurring in jejunal heterotopic pancreas.

CONCLUSION: We report a unique case of acute terminal pancreatitis occurring in the jejunal heterotopic pancreas. Unlike previously reported cases, acute pancreatitis was not found histologically in the ordinary pancreas. BACKGROUND: Heterotopic pancreas may show the same inflammatory or neoplastic changes, such as acute pancreatitis and adenocarcinoma, as those that occur in the ordinary pancreas. However, histologically proven acute pancreatitis occurring in heterotopic pancreas is very rare and only three reports have been described. METHODS: A 53-yr-old Japanese man died of hepatic failure, and autopsy was performed. RESULTS: Autopsy incidentally revealed heterotopic pancreas of the jejunum. Microscopically, focal acute pancreatitis was observed in the jejunal heterotopic pancreas, whereas the pancreas of the normal location showed no abnormality. In addition, no clinical evidence of pancreatic disease was noted before death. Therefore, we diagnosed this case as acute terminal pancreatitis occurring in the jejunal heterotopic pancreas.

Acute Disease↗
PubMed1992

The density, contour, and thickness of the pancreas in diabetics: CT findings in 57 patients.

Insulin has a trophic effect on pancreatic acinar tissue, so the pancreas might be expected to atrophy in persons who have diabetes. Accordingly, we analyzed the density, contour (smooth or lobulated), and thickness of the pancreas on CT scans of diabetic patients and compared the results with those in control subjects. The prevalence of pancreatic lobulation (incisurae deeper than 2 mm) and its correlation with age in diabetic and control subjects were determined. The thickness of the pancreas was measured at three levels (head, body, tail). Three groups of diabetic patients were examined: 20 insulin-dependent patients, 25 patients not treated with nor dependent on insulin, and 12 patients treated with but not dependent on insulin. A control group included 57 nondiabetic patients. The ages of the control subjects were similar to those of the diabetic patients. The statistical significance of the differences between groups of diabetic patients and control subjects was estimated by using Student's t test for the values of density and thickness and the chi 2-test for the prevalence of pancreatic lobulation. The density of the pancreas in diabetic patients and control subjects was not statistically different. Diabetic patients had increased lobulation of the pancreas. All parts of the pancreas tended to be smaller in diabetic patients, but the degree of reduction varied. It was modest in the patients not treated with insulin, pronounced in insulin-dependent patients, and intermediate in non-insulin-dependent, insulin-treated patients. Moreover, the size of the body was significantly reduced in all three groups, whereas the size of the pancreatic head was preserved in patients not treated with insulin. In conclusion, CT of the pancreas shows that although density in diabetic patients is normal, lobulation is increased. Reduction in size involves the body of the pancreas more than other parts of the gland and is more pronounced in insulin-treated diabetic patients. CT of the pancreas might be useful to predict which diabetic patients will require insulin therapy.

Adult↗
PubMed1989

Pregnancy after combined pancreas-kidney transplantation.

Four successful cases of pregnancy after combined pancreas-kidney transplantation at four different centers are summarized. The techniques used for the pancreas transplantations were duct obstruction in one patient and enteric exocrine diversion in two patients; in all three patients the insulin delivery was to the systemic circulation. In one patient exocrine diversion was to the stomach and the vascular anastomosis to the splenic vessels, thus accomplishing portal insulin delivery. Immunosuppression consisted of cyclosporin and prednisolone in two patients; cyclosporin alone in one patient; and cyclosporin, azathioprine, and prednisolone in one patient. In all a cesarean section was performed, due to deteriorating renal function in two patients, a fall in fetal growth in one patient, and fear of inducing pancreas-graft pancreatitis during normal delivery in one patient. In all four women, perfect metabolic control was retained throughout the pregnancy, and despite the proximity of the pancreas graft to the growing uterus in three of the women, the pancreas grafts did not suffer any damage during the pregnancy. However, in one patient the pancreas graft was lost in acute rejection after delivery. This pancreas had functioned normally for 3 yr before this occasion. Of the offspring, one was completely normal, one had a bilateral cataract, and two were small for date. The latter two subsequently showed normal growth development. At follow-up at 3, 5, 7, and 28 mo, all kidney grafts and three of the pancreas grafts remained functional. We conclude that after combined pancreas-kidney transplantation, successful conception and pregnancy can be obtained. Despite reduced islet mass (segmental grafts), normal metabolic control can be retained throughout the pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type I diabetic recipients.

To evaluate the metabolic consequences of pancreas transplantation with systemic venous drainage on beta-cell function, we examined insulin and C-peptide responses to glucose and arginine in type I (insulin-dependent) diabetic pancreas recipients (n = 30), nondiabetic kidney recipients (n = 8), and nondiabetic control subjects (n = 28). Basal insulin levels were 66 +/- 5 pM in control subjects, 204 +/- 18 pM in pancreas recipients (P less than 0.0001 vs. control), and 77 +/- 17 pM in kidney recipients. Acute insulin responses to glucose were 416 +/- 44 pM in control subjects, 763 +/- 91 pM in pancreas recipients (P less than 0.01 vs. control), and 589 +/- 113 pM in kidney recipients (NS vs. control). Basal and stimulated insulin levels in two pancreas recipients with portal venous drainage were normal. Integrated acute C-peptide responses were not statistically different (25.3 +/- 4.3 nM/min in pancreas recipients, 34.2 +/- 5.5 nM/min in kidney recipients, and 23.7 +/- 2.1 nM/min in control subjects). Similar insulin and C-peptide results were obtained with arginine stimulation, and both basal and glucose-stimulated insulin-C-peptide ratios in pancreas recipients were significantly greater than in control subjects. We conclude that recipients of pancreas allografts with systemic venous drainage have elevated basal and stimulated insulin levels and that these alterations are primarily due to alterations of first-pass hepatic insulin clearance, although insulin resistance secondary to immunosuppressive therapy (including prednisone) probably plays a contributing role. To avoid hyperinsulinemia and its possible long-term adverse consequences, transplantation of pancreas allografts into sites with portal rather than systemic venous drainage should be considered.

Adult↗
PubMed1986

Effects of age and diet on the development of the pancreas and the synthesis and secretion of pancreatic enzymes in the young pig.

Effects of age and diet composition on amylase, trypsin and chymotrypsin activities in the pancreas and intestinal contents, pancreas weights and body weights were determined from birth to 56 d. A total of 120 pigs, five to seven pigs/litter from 18 litters, were slaughtered at birth, 14, 27, 29, 31, 42 and 56 d. Litters were allotted to dietary treatments (corn-soy, A; corn-soy + 20% dried whey, B; corn-soy + 5% lard, C) and offered these diets as creep feed at 14 d. All pigs were weaned at 28 d, placed in elevated nursery pens and fed their respective diets. Total activities of amylase, trypsin and chymotrypsin in the pancreas and small intestine increased (P less than .05) with age. Both trypsin and amylase activities, measured per kilogram body weight or gram pancreas weight, were low at 29 d in the intestine and increased to 56 d. Pigs on diet B had the highest level of trypsin and chymotrypsin in the intestinal contents (P less than .05). Trypsin activity in the pancreas (units/kg body weight) was lowest (P less than .05) for pigs on diet B and highest (P less than .05) for those on diet C (units/g pancreas and units/kg body weight). Amylase activity (units/kg body weight) was lower (P less than .05) in the pancreas for pigs on diet B than for those on diets A and C. Pigs on diet A had lower (P less than .01) intestinal amylase activities than those on diets B and C. Enzyme activities in the intestinal contents and pancreas were low following weaning. In the pancreas, activities decreased at 31 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1996

Cholecystokinin-A and cholecystokinin-B/gastrin receptor mRNA expression in the gastrointestinal tract and pancreas of the rat and man. A polymerase chain reaction study.

BACKGROUND: Gastrin and cholecystokinin (CCK) are thought to exert trophic effects on the gastrointestinal tract and pancreas. Two types of receptors have been cloned, CCK-A and CCK-B/ gastrin. We have examined the occurrence of CCK-A and CCK-B receptor mRNA in the brain, digestive tract, pancreas, and kidney of the rat and man by Northern blot and reverse transcribed polymerase chain reaction (RT-PCR). METHODS: Total RNA was isolated from rat tissues and reverse transcribed into cDNA. cDNA from brain, kidney, and pancreas of the rat and man and from human whole stomach were commercially available. Northern blot and a PCR technique based on Taq polymerase-antibody interaction and using CCK-A and CCK-B receptor-specific primers, followed by Southern blot analysis, were the methods used. RESULTS: By means of Northern blots, CCK-A receptor mRNA was detected in rat fundus mucosa and pancreas but not in the remaining GI tract or brain. By means of RT-PCR, CCK-A receptor mRNA was demonstrated in the brain and the mucosa of the fundus, antrum, duodenum, and colon, kidney, pancreas and pancreatic islets. CCK-B receptor mRNA was detected by Northern blot analysis in the brain and the fundus mucosa but not in the rest of the digestive tract and not in the pancreas, pancreatic islets, or kidney. By RT-PCR, expression of CCK-B receptor mRNA could also be detected in antrum mucosa. In man, CCK-A receptor mRNA was detected in the brain, stomach, pancreas, and kidney, whereas CCK-B receptor mRNA was found in the brain, stomach, and pancreas but not in the kidney. Cloning and DNA-sequence analysis of the PCR-amplified rat and human CCK-A and CCK-B receptor DNA fragments, which cover the protein-encoding regions of the intracellular loop C3, showed complete sequence homology as compared with published rat and human sequences. CONCLUSIONS: It appears unlikely that CCK will have effects in the ileum, at least not effects mediated by CCK-A receptors. It also appears unlikely that physiologic concentrations of gastrin in the circulation will promote growth (or exert other effects) in the pancreas, duodenum, ileum, and colon, since CCK-B receptor mRNA is not expressed or is poorly expressed in these tissues.

Animals↗
PubMed1998

Effects of islet hormones on nerve-mediated and acetylcholine-evoked secretory responses in the isolated pancreas of normal and diabetic rats.

This study employs the pancreas of normal and diabetic rats to investigate the relationship between the endocrine and exocrine pancreas in the control of exocrine secretion employing enzyme and immunohistochemical and physiological techniques. Acetylcholine esterase (ACh-E) positive nerves were distributed in the interacinar regions of the pancreas lying close to the exocrine cells. There was no difference between the cholinergic innervation of the pancreas in normal and diabetic rat. Insulin (INS) immunopositive cells were observed in the peripheral and central portions of the Islet of Langerhans in the pancreas of normal rat. In the diabetic animals the number of INS-positive cells were decreased. In contrast, glucagon (GLU) and somatostatin (SOM)-immunopositive cells were identified mainly in the peripheral parts of the Islets of Langerhans and their numbers increased markedly in the diabetic pancreas. Insulin alone had no significant effect on amylase secretion in the normal pancreas whereas GLU and SOM evoked small increases in amylase out compared to basal. In contrast, the islet hormones have no detectable secretory effect on the diabetic pancreas compared to control. Both electrical field stimulation (EFS) of intrinsic secretomotor nerves and exogenous application of acetylcholine (ACh) resulted in marked increases in amylase secretion. In pancreatic acini and acinar cells ACh evoked dose-dependent increases in amylase release. In normal pancreatic segments a combination of either INS or GLU with EFS or ACh resulted in marked potentiation of amylase output. In contrast, SOM inhibited the EFS-evoked amylase output but enhanced the secretory response to ACh. In pancreatic acini and acinar cells from normal rat and in pancreatic segments from diabetic rats, the islet hormones had no potentiating effect on the ACh-evoked secretory response. Similarly, in the diabetic rat the islet hormone had no effect on EFS-evoked amylase output. In fura-2 loaded pancreatic acinar cells ACh-induced a marked increase in intracellular free calcium concentration [Ca2+]i compared to basal. Either INS or GLU, but not SOM, elicited a small increase in [Ca2+]i. Combining either INS or GLU with ACh resulted in a potentiation of [Ca2+]i compared with ACh alone. In contrast, SOM had no significant effect on the ACh-induced [Ca2+]i compared to the response obtained with ACh alone. In pancreatic acinar cells of diabetic rat ACh-elicited similar magnitude of [Ca2+]i compared to acinar cells of normal rat. However, when the islet hormones were combined with ACh there was no enhancement of [Ca2+]i compared to ACh alone. The results indicate that the potentiation of either EFS or ACh-evoked secretory responses by the islet hormones seem to occur only in pancreatic segments which have intact viable Islets of Langerhans and not in either acini and acinar cells or from the pancreas of diabetic rat. Moreover, it is apparent that cellular Ca2+ is involved with the interaction of ACh with either INS or GLU.

Acetylcholine↗
PubMed2006

[Application of computed tomography guided percutaneous fine-needle aspiration biopsy in examination of pancreas and Vater's ampulla].

OBJECTIVE: To evaluate the effects of computed tomography (CT) guided percutaneous fine-needle aspiration biopsy (FANB) in examination of pancreas and Vater's ampulla. METHODS: One hundred and six patients, 71 males and 35 females, aged 21 approximately 74, with lesions located in the pancreas and Vater's ampulla, 1.5 approximately 5 cm in size (< 3 cm in 32 cases and >or= 3 cm in 74 cases), underwent CT guided percutaneous FANB with 22-gauge needle (in 84 cases) or 20-gauge needle (in 22 cases) by anterior approach. The biopsy sites included the head of pancreas and ampulla (n = 70), body of pancreas (n = 24), and tail of pancreas (n = 12). The key points of FANB included selection of appropriate cross-section, entry of needle, and multiple insertion in fan-like fashion with fast puncture and aspiration. Pathological examination was done to all biopsy specimens. RESULTS: All lesions were safely accessed with an accuracy rate of 100% and without major complications. Pathological examination showed that 83 lesions were malignant, 5 of which were confirmed as false-positive, and 20 lesions were benign 2 of which were confirmed as false-negative, and 3 lesions were true-negative. The accuracy rates of diagnosis of malignant lesions and of diagnosis of benign lesion were 94% and 90% respectively (P > 0.05). The accuracy rate of diagnosis was 96% for the lesions >or= 3 cm was 96% and 88% for the lesions < 3 cm (P > 0.05). The accuracy rates of diagnosis were 93%, 92%, and 100% for the lesions located in the head of pancreas and ampulla of Vater, body of pancreas, and tail of pancreas (P > 0.05). CONCLUSION: CT guided percutaneous FANB is a safe and effective method for the diagnosis and differential diagnosis of lesions in the pancreas.

Adult↗
PubMed1990

Pancreas transplantation: report on United States results from United Network for Organ Sharing Registry with comparison to non-United States results from the International Registry.

From December 17, 1966 to December 31, 1990, 3,069 pancreas transplants worldwide (1,806 United States and 1,263 non-United States) were reported to the International Pancreas Transplant Registry, including 606 in 1990. The 2,871 pancreas transplants in the Registry data base as of October 31, 1990 were analyzed. Results worldwide improved in each of 5 successive eras. The recipient and pancreas graft functional survival rates at 1 year for all 1988 to 1990 cases (n = 1,415) were 91% and 68%, respectively. The effect of multiple variables on outcome was determined by analyzing the 2,037 cases in the International Registry data base since 1985. Worldwide, BD (n = 1,566) was used more frequently than DI (n = 327) or ED (n = 174) and was associated with a significantly higher (p less than 0.001) graft functional survival rate, at 1 year 65% versus 56% and 53%, respectively. Worldwide, SPK transplants (n = 1,644) were performed much more frequently than either PAK (n = 223), or PTA (n = 212). The pancreas graft functional survival rate was significantly higher (p less than 0.001) in the SPK than in the other 2 categories, at 1 year being 68% versus 45% and 37%, respectively. The kidney graft survival rate for all SPK cases at 1 year was 80%. Worldwide, a significant effect of HLA-DR matching was seen only in analysis of PTA, graft survival at 1 year being 54% in PTA recipients matched for 2 DR antigens (n = 13), 44% for 1 DR antigen (n = 63) and 29% for 0 DR antigens (n = 97) (p = 0,015 for 2 vs 0 DR). Worldwide, more than half of the pancreas grafts were preserved in UW solution (n = 1,111), and an increasing preservation length was not associated with a significant decrease in functional survival rates, at 1 year being 67%, 73%, 71%, and 60% for those stored less than 12 (n = 563), 12-24 (n = 416), 24-30 (n = 30), and greater than 30 (n = 5) hours. A separate analysis was performed on pancreas transplants in the United States reported to the UNOS Registry from its inception on October 1, 1987 to October 21, 1990 (n = 1,021). Almost all pancreas transplants in the United States during this period were by the BD technique (92%). The overall patient and pancreas graft survival rates were 92% and 72% at 1 year.(ABSTRACT TRUNCATED AT 400 WORDS)

Follow-Up Studies↗
PubMed1987

Pancreas divisum: incidence, detection, and clinical significance.

Pancreas divisum is a congenital anomaly in which the ventral and dorsal pancreas drain separately into the duodenum. It is the most common congenital variant of pancreatic ductal fusion and drainage anomalies. With widespread use of endoscopic retrograde cholangiopancreatography, pancreas divisum is being detected with increasing frequency. Ten cases of pancreas divisum detected among 500 endoscopic retrograde cholangiopancreatography examinations performed between 1979 and 1985 at our institution were critically analyzed. Patients with symptomatic pancreas divisum (group 1) were typically young (mean age 29 yr), usually female, and had no history of significant alcohol abuse. Those with incidental detection of pancreas divisum (group 2) were older (mean age 62 yr), usually male with hepatobiliary disease, and had a history of significant alcohol ingestion. The radiological feature of pancreas divisum is characterized by a short (1-6 cm) and thin (2 mm diameter) pancreatic duct (duct of Wirsung) that branches off into regular arborization and drains only the posterior part of the head of the pancreas. This appearance is quite typical; however, this may be simulated by other conditions such as previous pancreatic trauma, partial pancreatectomy, or pancreatitis with irreversible damage to the duct, pseudocyst, and pancreatic carcinoma. The differentiation between true and false pancreas divisum is important because of its clinical implications.

Adult↗
PubMedDate not supplied

Subtotal resection of the head of the pancreas preserving duodenum and vessels of pancreatic arcade.

We reported a procedure of duodenum-preserving subtotal pancreatectomy of the pancreas according to the precise anatomy of the pancreatoduodenal region, especially of the pancreaticoduodenal arteries which provide blood to the duodenum. After a complete Kocher's maneuver is performed, the pancreas is cut above the portal vein and removed from the third portion of the duodenum, followed by the removal of the posterior surface of the pancreas head from a connective tissue membrane. The main pancreatic duct is identified at its junction with the terminal portion of the bile duct from the posterior surface of the head of the pancreas and is cut at the junction. The pancreas is cut in the line of the ASPD. The reason we leave the part of the pancreas between the auodenum, ASPD and the common bile duct is that the artery toward the papilla of Vater runs along the right side of the common bile duct and would be difficult to be preserved with the removal of this part of the pancreas. The most important techniques of this procedure is to keep the connective tissue membrane of the posterior surface of the pancreas intact so as to preserve pancreaticoduodenal arteries and veins. Benign lesions as well as lowgrade malignancy of the head of the pancreas may be possible indications for this procedure.

Angiography↗
PubMed1995

[Function of pancreas transplants in increased metabolic stress].

Patients undergoing successful pancreas transplantation have normal glucose levels in the fasting and fed states and normal levels of hemoglobin A1c without use of exogenous inulin or any other medications for diabetes. In some of these patients, these measures have remained stable for more than 10 years. Additionally pancreas transplant recipients recover from short-term hypoglycemia produced by an intravenous pulse of insulin. However, metabolic success has been determined by relatively routine, unsophisticated tests such as oral and intravenous glucose tolerance tests or stimulation with intravenous arginine. These tests may not provide measures of the functional reserve of the pancreas, which is called on during periods of maximal stress. Consequently, we designed studies to ascertain beta and alpha cell performance in recipients of whole pancreas transplants and recipients of a segment of a living related donor. All recipients were recruited from the University of Minnesota Transplant Registry, Minneapolis, Minnesota. Successfully transplanted recipients were subjected to prolonged hyperglycemia to assess insulin secretory reserve using the method of glucose potentiation of arginine induced insulin secretion and to prolonged hypoglycemia to assess glucagon responsiveness and hepatic glucose production using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show that pancreas transplant recipients have markedly diminished insulin secretory reserve, a defect not evident with conventional tests of beta-cell function. No difference was found between the whole graft and segmental graft recipients. Pancreas transplantation restores the defective glucagon secretory response and enhances hepatic glucose production during prolonged hypoglycemia in subjects with type I diabetes. We conclude that pancreas transplantation does not completely restore beta-cell secretory reserve. This defect might be probably caused in part by cyclosporine and by the procedure involved in transplanting a cadaveric pancreas. Pancreas transplantation normalizes hypoglycemia-induced glucagon secretion and hepatic glucose production, thereby allowing for normalization of glucose recovery from hypoglycemia.

Diabetes Mellitus, Type 1↗
PubMed1996

Pancreas transplantation at the University of Maryland.

1. The University of Maryland pancreas transplant program was initiated in July 1991. Through December 1996, 230 pancreas transplants were performed (145 SPK, 64 PAK, 21 PTA). Overall one-year patient and graft survival rates were 95.5% and 78.9%, respectively. 2. The majority of pancreases have been transplanted simultaneously with a kidney. The one-year patient, pancreas and kidney survival rates for SPK transplants were 95.5%, 91.9%, and 82.5%, respectively. 3. Pancreas alone (PA = PAK or PTA) transplants have represented an increasing proportion of the total in recent years. Although the results of PA were previously inferior to SPK transplants, recent developments have made the outcomes equivalent. The advent of FK and MMF have sharply reduced graft losses due to irreversible rejection. Percutaneous pancreas biopsy now provides a safe and effective means to diagnose acute rejection in a timely manner. Anticoagulation protocols have markedly reduced the risk of idiopathic postoperative graft thrombosis. The most recent series of 71 PA cases at our center had a one-year graft survival rate of 75.8% overall, and 88.2% for the 61 technically successful ones. 4. The most widely practiced pancreas transplant technique in the US today includes bladder drainage of exocrine secretions. This results in a high incidence of bladder complications, which can be avoided by enteric exocrine drainage. The most recent series of pancreas transplants at the University of Maryland have been enteric drained, encompassing about half of all cases. Adoption of this technique has eliminated bladder complications, and has not been associated with an increase in anastomotic leaks, infectious complications or graft loss. 5. Most pancreas transplants have had systemic venous drainage via the iliac vein. We recently adopted the portal venous drainage technique, since it eliminates the peripheral hyperinsulinemia associated with systemic drainage, and may therefore improve lipid metabolism and possibly reduce the risk of progression of atherosclerosis. Early results have been favorable. 6. At present the major determinant of pancreas transplant outcome is donor quality. We have emphasized the importance of using pancreases free of fatty or fibrotic transformation, which have been skillfully procured from young, stable, non-obese donors.

Diabetes Mellitus, Type 1↗
PubMed1997

Effect of race on outcome following kidney and kidney-pancreas transplantation in type I diabetics: the South-Eastern Organ Procurement Foundation experience.

In this study we analyze the South-Eastern Organ Procurement Foundation (SEOPF) experience with kidney and kidney-pancreas transplantation in IDDM recipients and evaluate the impact of racial disparity on patient and graft outcome. Data obtained from 4413 kidney-alone and 884 pancreas transplants performed in White and Black type I diabetics at member institutions of SEOPF between 10/1/87 and 7/25/96 were analyzed. Survival data from 15,827 transplants performed during the same period of time in non-diabetics were available for comparison. A lesser proportion of pancreas recipients were Black compared to kidney-alone (12% vs 23%, p < 0.0005). Recipient race had no effect on patient survival in any of the groups studied. Kidney graft survival, on the other hand, was adversely affected by Black race in both non-diabetic and diabetic recipients of a kidney transplant but not in diabetics who received a combined pancreas-kidney transplant. As was the case for patient survival in diabetics, recipient race had no effect on pancreas graft survival. Cox Regression analysis showed that kidney-pancreas transplant (p = 0.034, RR = 0.49) and female recipient gender (p = 0.046, RR = 0.68) were associated with a lower risk of failure of the pancreas graft. The following factors were independent predictors of kidney graft outcome: Donor age (p = 0.0001, RR = 0.95), kidney-pancreas transplant (p = 0.0004, RR = 0.58), AB match (p = 0.001, RR = 0.86), DR match (p = 0.006, RR = 0.82), preservation time (p = 0.012, RR = 1.01), Black recipient race (p = 0.047, RR = 1.23) and living donor (p = 0.06, RR = 0.73). Our findings suggest that the effect of race on graft outcome observed in non-diabetic and, to a lesser extent, diabetic kidney-alone transplant recipients, is not present after kidney-pancreas transplantation.

ABO Blood-Group System↗
PubMed1997

Molecular diagnosis of pancreas carcinoma.

Cellular protooncogenes, tumor suppressor genes (antioncogenes), and DNA mismatch repair mutators are generally the key molecular genetic biomarkers undergoing alterations during carcinogenesis, i.e., activation of oncogenes, inactivation of tumor suppressors, and DNA mismatch repair gene defects are essential events in cancer causation. In pancreas cancer, high incidence of oncogene K-ras point mutations at the codon 12th is associated with premalignant and malignant transformation. Mutation in p53 tumor suppressor is also detected in pancreas adenocarcinoma. Concurrent loss of p53 and K-ras function may contribute to the clinical aggressiveness of pancreas cancer. Microsatellite instability and DNA mismatch repair defects may represent new mutator phenotype for pancreas carcinogenesis. Mutation of cell cycle regulators, such as inhibitor of CDK4 or p16 tumor suppressor gene, is a new molecular event in pancreas cancer. Mutation of cyclin-dependent kinases also may be involved in pancreas carcinogenesis. Loss or mutation of a new candidate tumor suppressor, DPC4 (deleted in pancreas carcinoma locus 4), is reported in pancreas cancer. The protein products of these gene mutations are potential tumor antigens, thus genotype expression can be detected by phenotype. Most of these emerging molecular genetic biomarkers are associated with regulation of cell growth and recognition, as well as gene expression, and may offer new insight into the cellular precursors to and genesis of pancreas cancer.

Biomarkers, Tumor↗