Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic analogues of CCK-4 in which Trp was replaced by D-Pro (peptide I), Thz (peptide II) and delta Pro (peptide III) have been studied for their insulin and glucagon releasing activities from the islets of Langerhans in vitro. Peptide I has been found to be the most potent insulin releaser among the three analogues and its activity is comparable to that of CCK-4. Unlike CCK-4, its three analogues (peptides I-III) do not stimulate the release of glucagon with basal concentration of glucose in the medium. However, with increasing glucose concentration, all the three analogues potentiate the glucose stimulus for insulin release.
Acta Diabetol Lat
PMID:Selective stimulation of insulin secretion by CCK-4 analogues having N-terminal modifications. 186 88

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) revealed a new mode of hypoglycemic action with a more rapid onset and a shorter duration of action than the sulfonylureas (SUs). Hypoglycemic mechanisms and glycemic control benefits were demonstrated in laboratory animals. The stimulatory effect of A-4166 on insulin release, in fasting dogs with a cannula into the portal vein, was more rapid than that of tolbutamide after oral administration. A-4166 stopped the stimulation of insulin secretion very quickly, whereas tolbutamide maintained an elevation in plasma insulin levels for at least 6 hours. In the case of A-4166, a counter-regulatory glucagon response was observed during recovery from hypoglycemia, but it was significantly inhibited by tolbutamide. Hyperglycemia induced by glucose loading was rapidly inhibited by A-4166 in normal rats, in genetically diabetic KK mice and in STZ-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. Also, repeated administration of A-4166 for 2 weeks enhanced insulin secretion in the same manner as a single administration in normal rats. In conclusion, A-4166 is a new type of oral hypoglycemic agent, having a rapid and short-term insulin secretory effect and no suppressive effect on the hypoglycemia-induced glucagon response. Oral therapy with A-4166 would be beneficial in supplementing endogenous insulin secretion and would exert ideal glycemic control in NIDDM patients.
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PMID:Possibility of ideal blood glucose control by a new oral hypoglycemic agent, N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166), and its stimulatory effect on insulin secretion in animals. 190 97

The effects of four different diets, a balanced (BD), a high protein (HP), a high fat (HF), and a high carbohydrate (HC) diet on glucose tolerance and pancreatic hormone secretion were compared during the ten-week period immediately after weaning in rats having glucose intolerance induced by streptozocin in the neonatal period (NSZ). Feeding HF or HC produced decrease in calorie intake and a delay in body weight increase. All NSZ rats showed glucose intolerance as adults; the HF rats showed a further deterioration of glucose tolerance and a decreased insulinogenic index after oral glucose loading. Plasma insulin levels of HC rats were lowest. The glucose-induced insulin and somatostatin secretion from the isolated perfused pancreas was almost identical in all four groups. The arginine-induced insulin and glucagon secretion was decreased in HF and HC rats, compared to both HP and BD rats, but somatostatin secretion was not. These results indicate that a high fat or high carbohydrate dietary environment is an important factor in the development of glucose intolerance and in the impairment of pancreatic hormone responsiveness to stimulation.
Acta Diabetol Lat
PMID:Effect of dietary environment on the development of impaired glucose tolerance and pancreatic hormone secretion in neonatal streptozocin-treated (NSZ) rats. 197 2

The aim of the present study was to evaluate whether the inhibitory effect on pancreatic A-cell exerted by hyperglycemic hyperinsulinemia and/or by somatostatin administration is impaired in human obesity. For this purpose plasma glucagon concentrations were measured in 8 obese and 8 nonobese nondiabetic subjects during a 4-h hyperglycemic clamp. Synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min during the third hour of the study. Fasting plasma glucagon was higher in obese than in nonobese subjects (242 +/- 32 vs 163 +/- 15 pg/ml, p less than 0.05) (mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma glucagon averaged 195 +/- 26 pg/ml in obese and 122 +/- 13 pg/ml in nonobese subjects (p less than 0.05), with a reduction of 19 +/- 3% in the former and 28 +/- 4% in the latter (p = n.s.). In both groups somatostatin infusion did not result in a further decrease in plasma glucagon, which averaged 192 +/- 27 pg/ml in obese and 123 +/- 16 pg/ml in nonobese subjects (p less than 0.05) in the 160-180 min period of the study. Also after discontinuing somatostatin infusion plasma glucagon levels did not change. These results suggest that in human obesity hyperglycemic hyperinsulinemia has a normal inhibitory effect on pancreatic A-cell and that somatostatin administration has no additive effect on hyperglycemia and hyperinsulinemia in either obese or nonobese nondiabetic subjects.
Acta Diabetol Lat
PMID:Plasma concentrations of glucagon during hyperglycemic clamp with or without somatostatin infusion in obese subjects. 198 86

Comparatively low level of serum insulin and tissue insulin resistance are characteristic of the stage of burn hypermetabolism. In order to evaluate the effect of tolbutamide in reducing burn hypermetabolism rate, 18 adult male rabbits weighing 1.8-2.5 Kg were subjected to 30% TBSA full thickness burns and randomized into treated and control groups. In the treated group, tolbutamide (90mg/Kg/day) was introduced into the stomach from 4 hours to 10 days postburn. Animals of both group were fed with specified food (protein 15%, glucose 80%) after burn. The values of serum glucose, insulin, glucagon, oxygen expenditure and other nutritional indices were measured before burn and 1, 3, 6, 10 days postburn. Their changes were as follows: (1) Serum glucose levels of the treated group were obviously lower than those of the control group (P less than 0.01). (2) Serum insulin levels and the ratio of I/G (insulin/glucagon) of the treated group were significantly higher than those of the control group (P less than 0.01). (3) The indices of cumulative N balance, oxygen expenditure, serum albumin in the treated group were better than that in the control (P less than 0.05-0.001). It is concluded that tolbutamide can reduce burn hypermetabolism probably through the following ways: 1. stimulation of the secretion of insulin and enhancement of the effect of insulin; 2. inhibition of the secretion of glucagon; 3. improvement in tissue insulin resistance and promotion of glucose utilization of skeletal muscles.
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PMID:[Tolbutamide and burn hypermetabolism]. 203 79

We examined the effect of the hypoglycemic drug linogliride on hormone release from the in vitro perfused rat pancreas. Linogliride stimulated insulin release in the absence of glucose either in the presence or absence of a physiological mixture of amino acids. In addition, linogliride inhibited amino acid-induced glucagon release. Half-maximal effects of linogliride on insulin and glucagon release were achieved at concentrations as low as 26 and 3 microM, respectively. The effects of linogliride on hormone release largely resembled those of tolbutamide. In the absence of amino acids, the stimulation of insulin release by linogliride or tolbutamide was transient. When the pancreas had been preperfused for 20 min with tolbutamide, linogliride no longer had an effect on hormone release. Likewise, tolbutamide remained without effect in pancreases preperfused with linogliride. These data suggest that linogliride and tolbutamide may have a similar mechanism of action.
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PMID:Effect of linogliride on hormone release from perfused rat pancreas. Fuel dependence and desensitization by tolbutamide. 206 Jul 24

The HLA haplotype and its relationships with clinical, biological and immunological parameters were analyzed in a group of 87 Spanish type 1 diabetic patients at the clinical onset of the disease. The frequency of HLA-B18, DR3 and DR4 antigens was significantly increased whereas DR2, DR5 and DR7 were decreased in comparison with 189 healthy unrelated controls without family history of diabetes. DR3 showed a maximum relative risk for diabetes (5.5) whereas DR4 had a lower one (4.0). HLA-DR4 patients were younger at the time of diagnosis than DR4 negative (16.7 vs 21.4 years). We found no statistically significant relationship between HLA antigens and the other variables studied including the presence of islet cell antibodies, complement fixing islet cell antibodies, insulin autoantibodies, organ-specific antibodies, fasting and maximal glucagon stimulated C-peptide levels, initial glycemia and glycosylated hemoglobin.
Acta Diabetol Lat
PMID:HLA antigens in Spanish type 1 diabetic population. Correlations with clinical, biological and autoimmune markers. 207 84

Secondary diabetes mellitus was the main abnormal finding in a young lean woman with benign extra-adrenal para-aortic norepinephrine and dopamine secreting pheochromocytoma. Glucose and insulin response to oral glucose and C-peptide secretion after glucagon i.v. were evaluated before and after alpha-blockade with phenoxybenzamine. Alpha-blocking treatment restored the inhibited basal and stimulated C-secretion but did not normalize glucose tolerance. After tumor removal metabolic abnormalities were normalized, confirming the role of endogenous catecholamine excess in the pathogenesis of our patient's glucose intolerance.
Acta Diabetol Lat
PMID:Diabetes mellitus as presenting feature in extra-adrenal pheochromocytoma: report of a case. 207 89

The effect of acute i.v. administration of 2.5 mg metoclopramide (MCP), an antidopaminergic agent with low serotoninergic activity, on blood insulin and glucose concentrations was studied in 9 healthy men. MCP was able to significantly decrease basal serum insulin levels (from 6.8 +/- 1.1 to 4.3 +/- 0.7 microU/ml in 120 min; p less than 0.025) with a parallel elevation in blood glucose (from 72.5 +/- 1.1 to 82.6 +/- 2.5 mg/dl in 120 min; p less than 0.01). These findings, which were not observed after placebo, and appeared not to be explained by the spontaneous occurrence of physiological oscillations of insulin and glucose plasma levels, are consistent with similar effects observed after administration of other antidopaminergic agents and with the stimulatory activity on insulin and glucagon release described during dopamine infusion in man.
Acta Diabetol Lat
PMID:Effect of acute administration of metoclopramide on insulin secretion in man. 218 88

The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.
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PMID:Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome. 218 84


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