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Biomedical subjects

T Kazumi

Publications and source records attributed to T Kazumi.

At least 91 records · Page 5Linked to original sources
PubMed1986

Triglyceride kinetics: effects of dietary glucose, sucrose, or fructose alone or with hyperinsulinemia.

The effects of different dietary sugars, with or without exogenously induced hyperinsulinemia, on rat plasma triglyceride kinetics have been studied. Glucose, sucrose, or fructose were supplied as 10% drinking solutions. The sugar-supplemented groups were each divided into subgroups, one receiving 6 U of insulin per day for 2 wk from intraperitoneally implanted minipumps and the other receiving none. The same degree of hyperglycemia and of endogenous hyperinsulinemia was seen in each sugar-supplemented group. Infusing exogenous insulin restored normoglycemia and produced more pronounced but equal hyperinsulinemia in each subgroup. In those rats that received no exogenous insulin, triglyceride production increased 18% in the sucrose-supplemented group and 20% in the fructose supplemented subgroups, but not at all in the glucose-supplemented subgroup. This 20% increase in triglyceride production in the fructose-supplemented subgroup was accompanied by a six times greater (120%) increase in triglyceride concentration. This suggested that dietary fructose not only increased triglyceride production, but also impaired triglyceride removal. Exogenously induced hyperinsulinemia further increased triglyceride production in those rats receiving dietary fructose, either as the monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. As exogenous insulin returned the triglyceride concentrations to normal in the fructose-supplemented rats, it also appeared to overcome any fructose-associated impairment of triglyceride removal.

Animals↗
PubMed1985

Changes in very low density lipoprotein particle size and production in response to sucrose feeding and hyperinsulinemia.

The effects of chronic (2 weeks) hyperinsulinemia on the production of very low density lipoprotein (VLDL) triglyceride and on VLDL particle size were examined. Hyperinsulinemia was induced by a constant sc infusion of 6 U porcine insulin/day from an osmotic minipump. To avoid profound hypoglycemia, these rats received chow plus 10% sucrose in their drinking water. Therefore, two control groups were examined; one receiving chow plus the same amount of sucrose (high carbohydrate control) and the other receiving chow only (chow control). The constant infusion model was compared to a previously reported model of hyperinsulinemia. In that model, NPH insulin was injected for 2 weeks twice daily in incrementally increasing doses (final dose, 6 U/day) into rats that were also fed chow and given 10% sucrose drinking water. Results with the injection model were similar to those previously reported: an increase in triglyceride production in face of a decrease in FFA, a minimal decrease in serum triglyceride, and some decrease in serum glucose. The infusion model produced the same increase in triglyceride production and decrease in fatty acid concentration. However, it differed in producing an increase in serum triglyceride and no change in serum glucose. The former suggested that in the infusion model triglyceride removal was not stimulated as much as in the injection model. Since there was no hypoglycemia in the infusion model, it was unlikely that VLDL changes were caused by an increase in counter regulatory hormones. VLDL particle size was increased in the high carbohydrate controls. This indicated that changes in sucrose supplementation led to the production of more triglyceride-filled VLDL particles. Hyperinsulinemia was not accompanied by any further increase in particle size. Thus, the hyperinsulinemia-induced increase in VLDL-triglyceride production was accompanied by an equivalent increase in VLDL particle production.

Animals↗
PubMed1984

Production of monoclonal antibodies to islet cell surface antigens using hybridization of spleen lymphocytes from non-obese diabetic mice.

Non-obese diabetic mice display a syndrome with dramatic clinical and pathological features similar to those of Type 1 (insulin-dependent) diabetes in man. Circulating autoantibodies to the surface of islet cells were demonstrated in some of these mice by a protein A radioligand assay. To produce monoclonal antibodies to islet cell surface antigens, therefore, we took the spleens of non-obese diabetic mice, transferred the spleen cells into non-immunized recipient mice, which were made immunologically incompetent by a large dose of X-irradiation, and then fused their lymphocytes with FO mouse myeloma cells. After screening the resultant hybrids, one stable hybridoma (3A4) that produced a monoclonal antibody (IgG1) specifically bound to the surface of islet cells was obtained. The purified monoclonal antibody was bound to the surface of transplantable Syrian golden hamster insulinoma cells sevenfold more than control antibody. Adsorption of the antibody on mouse spleen lymphocytes or thymocytes resulted in only a slight decrease in 125I-protein A binding to insulinoma cells. This antibody also reacted with the surface of mouse and rat islet cells, but not with that of rat spleen cells or hepatocytes. A spectrophotometric assay for peroxidase activity demonstrated that six times more peroxidase bound to insulinoma cells incubated with the antibody than to cells treated with control antibody. Furthermore, this antibody could be visually detected in the immunoenzymatic labelling of the surface of insulinoma cells. In summary, we have developed a novel method of producing monoclonal antibodies to the surface of islet cells for probing into the pathogenesis of Type 1 diabetes.

Animals↗
PubMed1984

Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide.

Pancreatic exocrine and endocrine function in the rat with islet cell tumors induced by streptozotocin and nicotinamide was studied in the in vitro isolated perfused pancreas. The tumor-bearing pancreas secreted significant amounts of insulin even at 2.8 mM glucose stimulation. Further, insulin response to 8.3 mM glucose stimulation was greater in the tumor-bearing pancreas than in the control. Not only endocrine, but also exocrine, disorders were found in the rat pancreas bearing islet cell tumors. In contrast to the increased response of insulin, amylase output in response to 0.1 ng/ml cerulein was significantly lower in the tumor-bearing than in the control pancreas, although there was no difference in pancreatic juice flows from both groups. These results suggest that enzyme secretory function of the pancreas with islet cell tumors may be suppressed in the presence of some interrelationship between the exocrine and endocrine portion of the pancreas with islet cell tumors.

Adenoma, Islet Cell↗
PubMed1983

Diabetes mellitus secondary to idiopathic chronic calcifying pancreatitis in an adolescent woman.

We describe the results of metabolic studies in a 17-year-old woman with diabetes mellitus which was the initial manifestation of idiopathic chronic calcifying pancreatitis (CCP). These studies were done on 2 occasions, 5 months and 5 years after the onset of diabetes, when her diabetes could be managed by glibenclamide and insulin, respectively. Five months after the onset of diabetes, oral glucose produced a small increase in insulin and a paradoxical rise in both glucagon immunoreactivity (GI) and growth hormone (GH). BY contrast, arginine-stimulated responses of the three hormones were normal. No increase in GI and a blunted rise in GH resulted from an insulin-induced decrease in blood glucose. Five years later, when CCP was demonstrated by roentogenologic examinations and tests of pancreatic exocrine function, oral glucose was followed by a flat and depressed response of C-peptide immunoreactivity and a markedly elevated response of gut glucagon-like-immunoreactivity (gut GLI). There were delayed and extremely low responses of pancreatic polypeptide to a test meal, irrespective whether or not her diabetes required treatment with insulin. These results demonstrate that CCP can cause diabetes in adolescents, as it does in adults, and that the adolescent woman described here had impaired responses of PP and gut GLI as well as insulin, GI and GH, especially to changes in blood glucose levels.

Adolescent↗
PubMed1982

Protection by nicotinamide against streptozotocin-induced reduction in pancreatic TRH.

The concentration of thyrotrophin-releasing hormone (TRH) immunoreactivity was determined in pancreatic islets and acini in the rat. In addition, time-course changes in TRH in response to an iv injection of streptozotocin (65 mg/kg body weight) with or without nicotinamide (500 mg/kg body weight) were examined in the whole pancreas. Furthermore, pancreatic TRH was measured in diabetic rats treated with insulin for 3 weeks. The TRH concentration in rat islets was 42-fold higher than in exocrine glands, indicating that the majority of pancreatic TRH is of islet origin. The mean concentration of pancreatic TRH decreased to 60 and 65% of the respective control values at 4 and 7 h after administration of streptozotocin, respectively. AT 24 h, it fell to 10% of control values without significant changes in TRH levels in the hypothalamus and gastrointestinal tract. In contrast, no significant change in pancreatic TRH was noted in rats given combined treatment with streptozotocin and nicotinamide. The injection of streptozotocin alone resulted in severe hypoglycaemia at 7 h and hyperglycaemia at 24 h, whereas neither resulted from the combined treatment. Insulin therapy had no influence on the decreased TRH concentrations in the diabetic pancreas. These results suggest that TRH may be localized to the B cells of pancreatic islets, and that the marked reduction in TRH in diabetic pancreases is not a metabolic consequence of insulin deficiency.

Animals↗
PubMed1981

Insulin and glucagon in rats with islet cell tumors induced by small doses of streptozotocin.

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 +/- 8.60 and 35.07 +/- 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 +/- 0.61 and 2.24 +/- 0.67 micrograms/g wet weight, respectively). These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.

Adenoma, Islet Cell↗
PubMed1981

Insulin release from the isolated perfused rat pancreas containing insulinomata induced by streptozotocin and nicotinamide: effects of glucose and responses to tumor removal.

The kinetics of insulin secretion in response to glucose were studied in the in vitro perfused rat pancreas before and after removal of islet cell tumors induced by streptozotocin and nicotinamide. In addition, insulin secretion before and after tumor removal was compared with that from normal pancreata before and after sham operations, respectively. Thus, the two pancreas preparations were subjected to repeated perfusions with glucose. Perfusion of pancreata containing tumors with 8.4 mM glucose resulted in biphasic release in a pattern similar to that of normal pancreas. However, both basal and stimulated insulin secretion of tumor-bearing pancreata were greater than either those of pancreata from which tumors had been excluded by ligature or those of normal pancreata before sham operation. A second increase in the concentration of glucose from 2.8 to 8.4 mM also produced a biphasic release of insulin from extratumoral pancreata as well as from sham-operated normal pancreata. However, the insulin secretory response to glucose of extratumoral pancreatic tissue was less than that of control pancreatic tissue. Our findings indicate that pancreatic islet cell tumors induced by streptozotocin and nicotinamide respond to glucose with typical biphasic insulin release. Thus, chemically induced rat insulinomata may provide a readily available and valuable model of insulin-secreting tissue, analogous to normal islets. Furthermore, our study suggests that the B cell function of pancreata containing tumors is inhibited by the preexisting tumor-induced hyperinsulinism or by its metabolic consequences.

Adenoma, Islet Cell↗
PubMed1980

Increase of pancreatic somatostatin concentration in early phases of streptozotocin diabetes in rats.

A small yet significant increase of immunoassayable pancreatic somatostatin concentration (0.107 +/- 0.005 vs. 0.156 +/- 0.017 microgram/g at 24 hr, p less than 0.05) was found in rats, 24 hr as well as 7 days after treatment with a diabetogenic dose of streptozotocin (65 mg/kg BW). These animals were characterized by marked decreases of insulin in the pancreas without any significant changes in pancreatic glucagon concentration. These results suggest that an abrupt deprivation of insulin from islets results in an elevation of pancreatic somatostatin concentration, and that glucagon in the pancreas plays a minor role in determining pancreatic somatostatin concentration in rats with insulin-deprived diabetes of short duration.

Animals↗
PubMed1980

Pancreatic islet cell tumors found in rats given alloxan and nicotinamide.

Morphological and biochemical studies were performed in pancreatic islet cell tumors found in rats given alloxan (40 mg/kg) and nicotinamide (305 mg/kg). Complete serial sections of the whole pancreas, combined with planimetric analysis, uncovered islet cell tumors in 5 of 7 rats which were killed 10 to 14 months after treatment. Hypoglycemia associated with hyperinsulinemia was found in a rat which developed a tumor which consisted of cells which reacted lightly with aldehyde fuchsin. Another rat developed a gross tumor which was composed of cells stained deeply with aldehyde fuchsin. However, flat insulin response to glucose associated with glucose intolerance was found in this rat. In addition to B cells, a few A and D cells were found within the two tumors. The present study suggests that pancreatic islet cell tumors found in rats given alloxan and nicotinamide are composed of at least three endocrine cell populations, although the majority of tumor cells are insulin-producing B cells.

Adenoma, Islet Cell↗
PubMed1980

Pancreatic insulin, glucagon and somatostatin concentrations in rats with islet cell tumors induced by streptozotocin.

Hyperinsulinemic and hypoglycemic rats with islet tumors induced by streptozotocin were shown to have significantly decreased immunoreactive insulin and somatostatin concentration (expressed as per g wet weight (w. wt) and content (expressed as per whole pancreas) in the pancreas surrounding the tumor as compared to those of age and weight adjusted controls. The pancreatic glucagon concentration of the former was significantly lower than that of the latter but no significant difference between glucagon content in the two groups was observed. Thus, inverse relationships were demonstrated between circulating insulin and somatostatin as well as insulin in the pancreas. It is suggested that a large amount of insulin in plasma results in a decrease in pancreatic insulin and somatostatin.

Adenoma, Islet Cell↗
PubMed1980

Portal somatostatin responds to intragastric glucose: effects of streptozotocin diabetes.

Changes in somatostatin levels in portal response to intragastric glucose loading were examined in normal controls and streptozotocin diabetic rats for one week duration. The mean (+/- SEM) basal level of somatostatin was more significantly elevated in diabetic rats (401 +/- 62 pg/ml) than in controls (171 +/- 13 pg/ml). However, no significant difference in somatostatin concentrations 30 min after glucose loading was found between diabetic and control animals (587 +/- 113 vs. 443 +/- 47 pg/ml). Glucose loading caused a significant elevation of somatostatin in controls, but not in diabetic rats. These results suggest a physiologic role of somatostatin in nutrient homeostasis, and that abnormalities in D cell function are present in streptozotocin diabetes of short duration.

Animals↗
PubMed1980

Effect of propranolol on glucose-induced insulin response in rats with insulinomas.

This paper describes an inhibitory effect of propranolol on insulin secretion in rats with pancreatic islet cell tumors which have been induced by streptozotocin (65 mg/kg body weight) and nicotinamide (500 mg/kg). Following glucose ingestion (3 g/kg), propranolol (4 mg/kg) was injected into the tumor-bearing rats. Plasma insulin decreased paradoxically despite an increase in blood glucoses. In contrast, propranolol did not suppress insulin secretion in normal rats. The drug was found to have no effect on glucagon secretion in either experimental or control animals during glucose load. This may suggest that the experimentally induced insulinoma in hypersensitive to propranolol for inhibiting insulin secretion.

Adenoma, Islet Cell↗
PubMed1980

Somatostatin concentration responds to arginine in portal plasma: effects of fasting, streptozotocin diabetes, and insulin administration in diabetic rats.

Changes of somatostatin concentration in response to a single i.v. injection of arginine (400 mg/kg body weight) were examined in extracted portal plasma of normal and diabetic rats in the fully fed state and after 24 h or fasting, as well as in diabetic rats treated with insulin for one week. In both normal and diabetic animals fasted for 24 h, the basal level of somatostatin declined but the magnitude of the arginine-induced elevation of somatostatin was not affected, suggesting a physiologic role of the tetradecapeptide in nutrient homeostasis. When compared with intact rats, diabetic animals were shown to have increased levels of somatostatin before and after arginine administration, both of which were attenuated by insulin replacement therapy. These findings suggest that alterations of D cell function in streptozotocin diabetes may be related to either insulin deficiency or its metabolic consequences.

Animals↗
PubMed1979

Insulin and glucagon relationships during aging in rats.

Oral glucose tolerance tests were performed under pentobarbital anesthesia in 43 male Wistar rats 2 to 18 months of age in order to determine if insulin and glucagon secretion are altered with aging. Although any linear correlation was not demonstrated between aging and blood glucose, plasma insulin or glucagon levels, post-glucose levels of blood glucose were significantly suppressed and those of plasma glucagon were significantly elevated at 4 to 6 months of age. No significant difference was found between young (2 months of age) and aged rats (12 to 14 and 17 to 18 months of age) in either blood glucose or plasma insulin levels during oral glucose load. On the other hand, post-glucose plasma glucagon levels of the aged rats were significantly higher than those of the young ones. Furthermore, comparisons of various kinds of indices among the different age groups, such as insulinogenic index, insulin/glucagon and so forth during oral glucose tolerance tests also indicate the significant alteration of glucagon secretion during aging process. It is concluded from the present data that glucose tolerance does not apparently deteriorate during aging process in rats but that glucagon responses to oral glucose administration are elevated with aging.

Aging↗