Biomedical subjects

S Efendic

Publications and source records attributed to S Efendic.

At least 91 records · Page 5Linked to original sources

PubMed1997

Galparan: a powerful insulin-releasing chimeric peptide acting at a novel site.

Galparan is a 27-amino acid long chimeric peptide, GWTLNSAGYLLGP-INLKALAALAKKIL amide, consisting of galanin-(1-13) linked to mastoparan amide via a peptide bond to provide the mastoparan and galanin effector parts of the molecules. Galparan (10 microM) powerfully stimulates insulin secretion from isolated rat pancreatic islets in a reversible and dose-dependent manner; the stimulation is 26-fold at 3.3 mM glucose and 6-fold at 16.7 mM glucose. Galparan also enhances insulin secretion to a similar extent from islets of diabetic GK rats. The stimulatory effect of galparan on insulin release is not directly dependent on extracellular Ca2+, nor can it be explained only by changes in free cytosolic Ca2+ concentrations. Furthermore, galparan is effective in evoking insulin release in B cells depolarized by 25 mM KCl when ATP-sensitive K+ channels are kept open by diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a distal site in the stimulus-secretion coupling of the B cell. This distal site is not identical to that used by mastoparan, as pertussis toxin pretreatment does not influence the insulinogenic effect of galparan. In conclusion, galparan evokes a large and reversible insulin secretion, acting at a yet unknown distal site and also promoting exocytosis in depolarized B cells from normal rats as well as diabetic GK rats.

Amino Acid Sequence↗

PubMed1996

Pituitary adenylate cyclase activating polypeptide (PACAP) redistributes the blood within the pancreas of anesthetized rats.

The aim of the study was to evaluate the effects of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) on splanchnic blood flow in anesthetized rats. For this purpose, either PACAP-38 dissolved in saline or saline alone was injected intravenously 5 (10 nmol/kg body weight (bw) PACAP-38) and 30 min (5 or 10 nmol/kg) before measurements. The blood flow to the whole pancreas, islets, duodenum and colon was then measured with a microsphere technique. The higher dose of PACAP-38 slightly increased blood glucose concentrations at both 5 and 30 min after administration, whereas the lower had no effect. Both doses of PACAP-38 induced a transient initial decrease in mean arterial blood pressure. The lower dose of PACAP-38 decreased fractional islet blood flow 30 min after administration, but did not affect the other blood flows. The higher dose of the peptide (10 nmol/kg bw) caused an increase in whole pancreatic blood flow at both 5 and 30 min after administration, whereas islet blood flow was only increased at the former time. At both time points PACAP-38 redistributed the blood flow within the pancreas in favour of the exocrine pancreas. This resulted in a decreased fractional islet blood flow, i.e., the fraction of whole pancreatic blood flow diverted through the islets. At 5 min after PACAP-38 administration duodenal blood flow was decreased, whereas after 30 min no effects on duodenal or colonic blood flow were observed. Administration of a VIP antagonist intravenously (20 nmol/kg bw) decreased the PACAP-38-induced pancreatic blood flow increase and intrapancreatic redistribution. When only the VIP antagonist was given both pancreatic and islet blood decreased in concert. It is concluded that administration of PACAP-38 induces a blood flow increase in the pancreas, preferably in the exocrine parts of the gland, by actions mediated by PACAP-38 receptors shared with VIP.

Amino Acid Sequence↗

PubMed1996

Daytime glibenclamide and bedtime NPH insulin compared to intensive insulin treatment in secondary sulphonylurea failure: a 1-year follow-up.

The aim of this study was to compare the metabolic effects of a combination of daytime glibenclamide and evening NPH insulin with intensive insulin treatment (rapid acting insulin before meals and NPH insulin at bedtime) in patients exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese NIDDM patients (BMI 25.6 +/- 0.5) were randomized after 6 weeks of intensive insulin treatment to either a combination treatment (CT, n = 20) or continued intensive insulin treatment (IT, n = 19). There were no differences between the two groups in age, diabetes duration, BMI, HbA1c, or basal and glucagon stimulated C-peptide. The patients were followed for 1 year and the findings were analysed on an intent to treat basis. Two patients in the CT group were excluded after 2 and 6 months, respectively, due to unacceptably high postprandial glucose values. There was a significant difference in HbA1c between the CT and IT groups at 6 months (8.2 +/- 0.2, n = 19, vs 6.8 +/- 0.4%, n = 19, p < 0.001)), but not at 12 months (7.8 +/- 0.3, n = 18, vs 7.5 +/- 0.4%, n = 19). After the initial intensive insulin treatment, BMI was constant in the CT group but increased significantly at 6 and 12 months in the IT group. We conclude that both treatments are associated with a marked and long-term improvement of glycaemic control. The intensive insulin treatment leads to a more pronounced weight increase which in the long run might have negative effect on overall metabolic control. Therefore, the combination treatment together with intensified education and dietary advice should be regarded as the initial treatment of choice for oral agent failure in moderately obese NIDDM patients.

Aged↗

PubMed1996

Pancreas size and insulin secretion: lack of association in non-diabetic subjects.

Both type 1 and type 2 diabetes mellitus are associated with reduced pancreatic size. This could be caused by insulinopenia with loss of a trophic insulin effect and/or other factors associated with a diabetic state. To investigate the role of long-term moderate insulinemia per se, we compared the pancreatic size in healthy subjects with documented low (n = 5) and high (n = 5) insulin secretion. Insulin responses to a glucose clamp (11 mM) procedure were threefold higher in the high insulin responders (HIR) than low insulin responders (LIR). Age, body mass index (BMI), and blood glucose were similar between groups. Computed tomography showed no difference in total pancreatic size (total pancreas volume 84.8 +/- 29.4 ml in LIR, 79.8 +/- 8.4 ml in HIR; NS) nor in the size of various parts (caput, corpus, or cauda). We conclude that moderate hypoinsulinemia of long duration does not affect the pancreatic size.

Adult↗

PubMed1996

A moderate decline in specific activity does not lead to an underestimation of hepatic glucose production during a glucose clamp.

We have previously shown that modeling errors lead to underestimation of hepatic glucose production (HGP) during glucose clamps when specific activity (SA) declines markedly. We wished to assess whether the failure to keep SA constant substantially affects calculation of HGP during insulin infusion when glucose requirements to maintain the glucose clamp are moderate. Therefore, 150-minute hyperinsulinemic (5.4 pmol - kg (-1) - min (-1) clamps were performed in depancreatized dogs that were maintained hyperglycemic (approximately 10 mmol/L with either (l) unlabeled glucose infusate (COLD Ginf, n = 5) or (2) labeled glucose infusate (HOT Ginf, n = 6) containing high-performance liquid chromatography (HPLC purified [6-3H]glucose. Insulinemia and glucagonemia were similar between the two groups. Additionally, glucose infusion rates were equivalent with COLD and HOT Ginf, indicating comparable insulin effects on overall glucose metabolism. The SA decreased a maximum of 32% with COLD Ginf, but remained constant with HOT Ginf. HGP was suppressed equally with COLD or HOT Ginf treatments at each time point during the clamp (mean suppression during last hour of clamp, 69% +/- 4% and 69% +/- 5%, P = NS, COLD and HOT Ginf, respectively). We conclude that when glucose requirements are moderate and SA changes slowly, as in the diabetic dog, it is not necessary to keep SA perfectly constant to avoid significant modeling errors when calculating HPG during hyperinsulinemic clamps.

Animals↗

PubMed1996

Glucagon response to hypoglycemia is improved by insulin-independent restoration of normoglycemia in diabetic rats.

The aim of this study was to determine whether the impaired glucagon response to insulin-induced hypoglycemia in the diabetic rat can be improved by correction of hyperglycemia independent of insulin. Four groups of age-matched male Sprague-Dawley rats (246 +/- 13 g BW) were studied: 1) normal controls (NC; n = 7); 2) diabetic, untreated (DU; n = 6); 3) diabetic, treated for 5-7 days using sustained release (2-3 U/day) insulin implants (DI; n = 6); and 4) diabetic, treated for 3-4 days with phlorizin (0.4 g/kg), given sc twice daily (DP; n = 7). Diabetes was induced by a single injection of streptozotocin (65 mg/kg). Basal plasma glucose was 7.4 +/- 0.3 mM in NC, but rose to 14.5 +/- 2.2 mM in DU. Basal hyperglycemia was corrected with phlorizin and insulin treatments (5.5 +/- 0.5 and 6.7 +/- 0.8 mM, respectively). NC rats responded to insulin-induced hypoglycemia with a rapid and marked increase in glucagon (peak, 2059 +/- 311 pg/ml). The glucagon response was blunted in DU (635 +/- 180 pg/ml) and was partially improved by prolonged normalization of glycemia in DP (1335 +/- 295 pg/ml; P < 0.05). Plasma somatostatin levels in all diabetic groups were 2- to 3-fold higher in the basal state, but were not different during hypoglycemia, than those in NC rats. Compared to levels in NC rats, diabetes resulted in decreased insulin, but elevated glucagon and somatostatin concentrations in the pancreatic tissue. Treatment with both insulin and phlorizin reversed the changes in the pancreatic content of both glucagon and somatostatin. Pancreatic proglucagon messenger RNA did not show significant differences among the four groups in either state. Insulin treatment in the DI group resulted in a delayed and much smaller increase in the glucagon response (740 +/- 138 pg/ml) to hypoglycemia despite normalization of glycemia. We, therefore, conclude that in streptozotocin-diabetic rats, the impaired glucagon responsiveness to hypoglycemia is significantly improved by insulin-independent correction of hyperglycemia, suggesting the importance of normoglycemia per se in maintaining, at least in part, the glucose sensitivity of pancreatic alpha-cells.

Animals↗

PubMed1996

Normal hepatic insulin sensitivity in lean, mild noninsulin-dependent diabetic patients.

We studied hepatic and extrahepatic insulin sensitivity and insulin release in seven nonobese patients with mild noninsulin-dependent diabetes mellitus (NIDDM) and 10 control subjects, matched for age, body mass index, and physical fitness. Glucose turnover was studied during sequential hyperinsulinemic euglycemic clamps (insulin infusion, 0.25 and 1.0 mU/kg BW.min), applying the hot-GINF (tracer-enriched glucose infusion) technique and using [6-3H]glucose. Hepatic glucose production was lower in hyperglycemic NIDDM patients during the basal period (P < 0.01), but was equivalent at similar glucose and insulin levels attained during both clamps. In contrast, during the low and high insulin clamps, glucose utilization was lower in NIDDM [14.90 +/- 1.00 vs. 17.24 +/- 0.83 (P < 0.01) and 41.37 +/- 3.05 vs. 50.54 +/- 3.61 mumol/kg BW.min (P < 0.01)]. Accordingly, the glucose infusion rate necessary to maintain euglycemia was lower in NIDDM [7.72 +/- 2.00 vs. 10.68 +/- 1.17 (P < 0.05) and 42.14 +/- 4.50 vs. 51.60 +/- 4.28 mumol/kg BW.min (P < 0.01)]. There was, however, a considerable overlap between patients and controls in the parameters describing insulin sensitivity. The insulin response to orally administered glucose as well as that to a standardized glucose infusion test (GIT) were diminished in NIDDM [average incremental insulin secretion during an oral glucose tolerance test, 88 +/- 28 vs. 251 +/- 50 pmol/L.min (P < 0.05); during first 10 min of GIT, 7 +/- 16 vs. 234 +/- 29 pmol/L.min (P < 0.001)]. There was no overlap in acute phase insulin secretion during the GIT between the groups. In conclusion, nonobese, mild NIDDM patients showed no impairment in hepatic, but a slight reduction in extrahepatic insulin sensitivity, with extensive overlap between diabetic and control subjects. In contrast, impairment of insulin release was very pronounced and without overlap.

Adult↗

PubMed1996

The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients.

OBJECTIVE: To investigate the long-term antidiabetogenic effect of glucagon-like peptide 1 (GLP-1) and its influence on diabetic dyslipoproteinemia, patients with NIDDM were treated with GLP-1 subcutaneously for 1 week. RESEARCH DESIGN AND METHODS: Twelve patients participated in the study. The 1st week of the study, all of them were on intensive insulin treatment and from day 8, four were randomized to a control group continuing with insulin, and eight to a treatment group where GLP-1 was given at meals together with regular insulin from day 8 to 12. On days 13 and 14, they were only given GLP-1 at meals. NPH insulin at bedtime was given throughout the study. RESULTS: In the GLP-1-treated patients, the doses of regular insulin, given to keep a satisfactory blood glucose control, were reduced compared with treatment with insulin only. GLP-1 virtually inhibited the early increase in blood glucose after the meals, whereas an increase of approximately 2 mmol was seen during an optimized insulin treatment. In agreement with the short half-life of the peptide, 2-h postprandial plasma insulin levels were significantly decreased both at day 12 and 14, suggesting that there was not enough GLP-1 left to stimulate endogenous insulin release and compensate for the decrease in the dose of exogenous insulin. Therefore, the effect of GLP-1 was lost before the next meal, resulting in increased preprandial blood glucose values at lunch and dinner. The concentration of VLDL triglycerides decreased already during the 1st week. This decrease persisted during the 2nd week when GLP-1 was included in the treatment. No changes were observed in the levels of LDL and HDL cholesterol. The LDL particle diameter increased from a mean of 22.3 to 22.6 nm (P < 0.01) in response to insulin treatment. A further increment to 22.9 nm (P < 0.05) was seen after GLP-1 treatment. The LDL particle size did not change in the control group. Lipoprotein lipase activity was decreased by 27% and hepatic lipase was reduced by 13% in the GLP-1-treated group. CONCLUSIONS: We confirm the antidiabetogenic effect of GLP-1 in NIDDM patients. This effect was maintained during 7 days, which implies that the patients did not develop tolerance during this treatment period. Intensive insulin treatment, leading to normotriglyceridemia, increased the mean LDL particle diameter, which is likely to lower the risk of future coronary heart disease in patients with NIDDM. Furthermore, an additive effect of GLP-1 is indicated. Hence, this study gives additional evidence that GLP-1 may be useful as an agent for treating NIDDM.

Blood Glucose↗

PubMed1996

Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas.

OBJECTIVE: To investigate the acute effects of glibenclamide and glucagon-like peptide I (GLP-I) and their combination in perfused isolated rat pancreas and in patients with secondary failure to sulfonylureas. RESEARCH DESIGN AND METHODS: Rat islets were perfused with 10 nmol/l GLP-I in combination with 2 mumol/l glibenclamide. In human experiments, GLP-I (0.75 pmol. kg-1.min-1) was given as a continuous infusion during 240 min, while glibenclamide (3.5 mg) was administered orally. Eight patients participated in the study (age 57.6 +/- 2.7 years, BMI 28.7 +/- 1.5 kg/m2, mean +/- SE). In all subjects, blood glucose was first normalized by insulin infusion administered by an artificial pancreas (Biostator). RESULTS: GLP-I increased the insulinotropic effect of glibenclamide fourfold in the perfused rat pancreas. In human experiments, treatment with GLP-I alone and in combination with glibenclamide significantly decreased basal glucose levels (5.1 +/- 0.4 and 4.5 +/- 0.1 vs. 6.0 +/- 0.3 mmol/l, P < 0.01), while with only glibenclamide, glucose concentrations remained unchanged. GLP-I markedly decreased total integrated glucose response to the meal (353 +/- 60 vs. 724 +/- 91 mmol.l-1. min-1, area under the curve [AUC] [-30-180 min], P < 0.02), whereas glibenclamide had no effect (598 +/- 101 mmol.l-1. min-1, AUC [-30-180 min], NS). The combined treatment further enhanced the glucose lowering effect of GLP-I (138 +/- 24 mmol. l-1.min, AUC [-30-180 min], P < 0.001). GLP-I, glibenclamide, and combined treat-stimulated meal-induced insulin release as reflected by insulinogenic indexes (control 1.44 +/- 0.4; GLP-I 6.3 +/- 1.6, P < 0.01; glibenclamide 6.8 +/- 2.1, P < 0.01; combination 20.7 +/- 5.0, P < 0.001). GLP-I inhibited basal but not postprandial glucagon responses. Using paracetamol as a marker for gastric emptying rate of the test meal, treatment with GLP-I decreased gastric emptying at 180 min by approximately 50% compared with the control subjects (P < 0.01). CONCLUSIONS: In acute experiments on overweight patients with NIDDM, GLP-I exerted a marked antidiabetogenic action on the basal and postprandial state. The peptide stimulated insulin, suppressed basal glucagon release, and prolonged gastric emptying. The glucose-lowering effect of GLP-I was further enhanced by glibenclamide. This action may be at least partially accounted for by a synergistic effect of these two compounds on insulin release. Glibenclamide per se enhanced postprandial but not basal insulin release and exerted a less pronounced antidiabetogenic effect compared with GLP-I.

Analysis of Variance↗

PubMed1995

Relationship between insulin responses to D-glucose and to L-arginine in women with a history of gestational diabetes.

The relationship between insulin responses to glucose and to arginine was studied in non-obese women with previous gestational diabetes (PGD). One group, n = 10, had normal glucose tolerance (NGT) by WHO criteria and another, n = 8, had impaired glucose tolerance (IGT). A third group of women without PGD, n = 12, was also studied. A hyperglycaemic clamp (blood glucose level 11 mM) and an arginine stimulation test (150 mg/kg L-arginine followed by 10 mg/kg.min) were performed on separate days. The ratios of arginine to glucose responses 0-10 min differed: they were 1.00 for non-PGD, 1.29 for NGT and 1.46 for IGT (P < 0.02 vs non-PGD). A further difference between groups was the ratio between first- and second-phase glucose-induced insulin secretion, which was significantly decreased in IGT, 0.72, compared with NGT, 0.98 (P < 0.01), and non-PGD, 1.05 (P < 0.005). However, within each group insulin responses 0-10 min to glucose and arginine were strongly correlated: for NGT (r = 0.75, P < 0.05), for IGT (r = 0.85, P < 0.01) and for women without PGD (r = 0.69, P < 0.05). Insulin sensitivity, as assessed by the M/I ratio, was non-significantly decreased in IGT (0.18 +/- 0.03 mg/kg.min per mU/l vs 0.26 +/- 0.03 in NGT and 0.28 +/- 0.03 in non-PGD, P < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

PubMed1995

Pancreatic polypeptide and splanchnic blood flow in anesthetized rats.

The aim of the study was to evaluate the effects of pancreatic polypeptide (PP) on splanchnic blood flow in anesthetized rats. For this purpose, either PP dissolved in saline (225, 450, or 900 pmol/kg body weight/h) or saline alone was infused at a rate of 2 ml/h for 30 min. Immediately after the infusion the blood flow to the whole pancreas, islets, duodenum, and colon was measured with a microsphere technique. The highest dose of PP caused a small decrease in mean arterial blood pressure. The two lowest doses decreased duodenal blood flow, but did not affect the blood perfusion to the other investigated organs. The highest dose of PP decreased the blood flow to the pancreas, islets, and duodenum, did not affect colonic blood flow. No change in the fraction of whole pancreatic blood flow diverted through the islets could be seen after PP administration. It is concluded that administration of high doses of PP induces a general splanchnic vasoconstriction.

Anesthesia↗

PubMed1995

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.

OBJECTIVES: We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND: Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS: A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS: The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

Aged↗

PubMed1995

Disturbed anabolic hormonal patterns in burned patients: the relation to glucagon.

OBJECTIVE: Complex changes in the anabolic regulators of metabolism occur after major injury. We have studied the time course for IGF-I and IGFBP-1 after burn injury and their relations to circulating levels of other anabolic and catabolic hormones. The hormonal patterns during the onset of sepsis were also investigated. PATIENTS: Eight patients (age 36 (6) years, mean (SEM)) with major burn injury (burn area 42 (6) %) were studied. The first 2 days since the burn were used for rehydration therapy (rehydration period), after which a complete total parenteral nutrition (TPN) period was initiated. Seven positive blood cultures, during the study period. Six of the eight survived. MEASUREMENTS: The hormonal changes determined in the morning during the first 7 days after the burn and from day 22 to 24 were investigated. The superimposed effects of sepsis were studied by normalizing all data to the day of positive blood cultures and clinical onset of sepsis. RESULTS: On admission, plasma levels of glucagon, IGFBP-1 and GH were elevated while levels of IGF-I were low. During the first week after the burn, morning levels of glucagon and insulin increased while levels of GH and IGF-I decreased. GH levels were still elevated compared to healthy subjects. Despite the increase in insulin levels, IGFBP-1 remained elevated. Three weeks after the burn injury, IGF-I levels were increased but still markedly below normal, while IGFBP-1 levels remained unchanged. Persistent elevations of insulin levels were combined with reductions in glucagon levels. Admission levels of IGFBP-1 correlated to nitrogen loss (negative nitrogen balance) during the first 24 hours after the burn (r = 0.84, P < 0.05). A correlation between negative nitrogen balance and glucagon levels was found during early catabolic period in the rehydration period (i.e. days 2-3, r = 0.84, P < 0.01). The relative change in IGFBP-1 levels in the rehydration period correlated to changes in glucagon levels (days 2-3 vs admission, r = 0.85, P < 0.05). The insulin/glucagon molar ratio correlated to the IGF-I/IGFBP-1 ratio during both the rehydration period (days 2-3, r = 0.77, P < 0.05) and the third week after the burn (r = 0.77, P < 0.05). During the most catabolic phase in the first week after the burn (TPN period) there was an inverse relation between IGF-I and IGFBP-I and glucagon (r = 0.83, P < 0.05). During the less catabolic third week after the burn, an inverse correlation was found between IGF-I and glucagon (r = -0.83, P < 0.05). Sepsis, superimposed upon the burn trauma, was associated with transient elevations in IGFBP-1 and reductions in insulin despite elevated levels of glucose and a further 50% increase in nitrogen losses. CONCLUSIONS: The present findings show that marked changes is important anabolic regulating factors occur after major burn injury. Uncoupling of the GH-IGF-I axis, and the attenuation of the inhibitory effects of insulin on IGFBP-1, both contribute to the reduction in IGF-I levels and bioavailability, factors which may play an important role in post injury metabolism. Furthermore, these data suggest that the catabolic hormones (catecholamines, cortisol and glucagon), primarily glucagon seem to be involved in the modulation of IGF-I and IGFBP-1 levels following burn injury.

Adult↗

PubMed1995

Evidence that increased glucose cycling in islets of diabetic ob/ob mice is a primary feature of the disease.

Glucose cycling (GC) is increased in pancreatic islets from hyperglycemic 6-mo-old ob/ob mice. We determined whether normalization of glycemia alters islet GC and insulin release in response to glucose as well as oxidation and utilization of the glucose. Mice were treated with phlorizin in dimethyl sulfoxide (DMSO) for 10 days, which resulted in normalization of blood glucose concentrations. Controls received DMSO. The mice were fasted overnight and killed, and their islets were isolated for measurements of insulin release at 5.5 and 16.7 mM glucose and at 16.7 mM glucose plus 10 mM arginine. GC was measured by the incorporation of 3H from 3H2O into carbon 2 of glucose, glucose oxidation by the yield of 14CO2 from [U-14C]glucose, and glucose utilization by the yield of 3H2O from [5-3H]glucose. Phlorizin treatment did not alter the response of insulin to glucose and to glucose plus arginine. GC was 30% in control and phlorizin-treated animals. Glucose oxidation and utilization were also the same in both groups. In fed 10- to 12-mo-old mice exhibiting a broad range of blood glucose levels, there was no correlation between GC and either insulin release or glucose concentrations. Thus the islets of ob/ob mice exhibit an increased rate of GC regardless of glycemia. This indicates that the increased rate of GC is an important characteristic of the diabetic syndrome in these animals and not simply secondary to hyperglycemia.

Animals↗

PubMed1994

Generalized presence of a PEC-60-like peptide in catecholamine neurones.

PEC-60, a 60-residue intestinal peptide structurally related to the pancreatic secretory type of trypsin inhibitor, has been isolated, characterized and molecularly cloned. It shows biological activity as a hormone in both the gastrointestinal tract and in the immune system. We now report immunohistochemical evidence suggesting its neural localization exclusively within central and peripheral catecholamine (CA) neurones. PEC-60-like immunoreactivity was present in cell bodies, dendrites and nerve terminals of virtually all catecholamine neurones examined and including the noradrenergic gland cells of the adrenal medulla. PEC-60-like immunoreactivity was not seen, however, within the tyrosine hydroxylase-positive but CA-negative arcuate neurones producing growth hormone releasing hormone. The findings open up the possibility that a PEC-60-like peptide may represent a generalized co-transmitter in the peripheral and central CA neurones.

Animals↗

PubMed1994

A porcine gut polypeptide identical to the pancreatic hormone PP (pancreatic polypeptide).

A peptide hormone has been isolated from porcine intestine. Its primary structure was found to consist of 36 amino acid residues in a sequence identical to that of the porcine pancreatic polypeptide, previously not isolated from intestines or a tissue other than pancreas. The gut polypeptide significantly suppresses glucose-induced insulin secretion in vitro. Using an immunohistochemical technique, we also identified cells in the porcine gastrointestinal tract that were immunoreactive with pancreatic polypeptide. The immunoreactivity disappeared after absorption with the isolated gut polypeptide or synthetic human pancreatic polypeptide.

Animals↗

PubMed1994

Insulin resistance after abdominal surgery.

A study was carried out to determine the time course and degree of postoperative insulin resistance in patients undergoing elective abdominal surgery. Mean(s.e.m.) insulin sensitivity was determined before and on the first (n = 10), fifth, ninth and 20th (n = 5) days after elective open cholecystectomy using the normoglycaemic (4.7(0.1) mmol/l), hyperinsulinaemic (402(12)pmol/l) glucose clamp technique. Preoperative insulin sensitivity expressed as the M value varied from 2.3 to 8.2 mg per kg per min. The relative reduction in insulin sensitivity was most pronounced on the first day after surgery, at a mean(s.e.m.) of 54(2) per cent. Thereafter, a large variation between individuals was found during the course of recovery, and insulin sensitivity returned to normal 20 days after operation. On the first day after surgery, plasma concentrations of glucose, C peptide, noradrenaline and glucagon were slightly but significantly higher than before operation (P < 0.05), whereas insulin, growth hormone, cortisol and adrenaline levels were unaltered. Marked insulin resistance thus develops after elective upper abdominal surgery and persists for at least 5 days after operation. Factors other than simultaneous changes in levels of the hormones studied seem to regulate the maintenance of postoperative insulin resistance.

Adult↗

PubMed1994

Oscillations in cytoplasmic free calcium concentration in human pancreatic islets from subjects with normal and impaired glucose tolerance.

Plasma insulin levels in healthy subjects oscillate and non-insulin-dependent diabetic patients display an irregular pattern of such oscillations. Since an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the pancreatic beta cell is the major stimulus for insulin release, this study was undertaken to investigate the dynamics of electrical activity, [Ca2+]i-changes and insulin release, in stimulated islets from subjects of varying glucose tolerance. In four patients it was possible to investigate more than one of these three parameters. Stimulation of pancreatic islets with glucose and tolbutamide sometimes resulted in the appearance of oscillations in [Ca2+]i, lasting 2-3 min. Such oscillations were observed even in some islets from patients with impaired glucose tolerance. In one islet from a diabetic patient there was no response to glucose, whereas that islet displayed [Ca2+]i-oscillations in response to tolbutamide, suggesting that sulphonylurea treatment can mimic the complex pattern of glucose-induced [Ca2+]i-oscillations. We also, for the first time, made patch-clamp recordings of membrane currents in beta-cells in situ in the islet. Stimulation with glucose and tolbutamide resulted in depolarization and appearance of action potentials. The islet preparations responded to stimulation with a number of different secretagogues with release of insulin. The present study shows that human islets can respond to stimulation with glucose and sulphonylurea with oscillations in [Ca2+]i, which is the signal probably underlying the oscillations in plasma insulin levels observed in healthy subjects. Interestingly, even subjects with impaired glucose tolerance had islets that responded with oscillations in [Ca2+]i upon glucose stimulation, although it is not known to what extent the response of these islets was representative of most islets in these patients.

Aged↗