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)

The intravenous infusion of prostaglandin (PG) E1, E2, and A1 into normal rats at a dose of 2 mug/min significantly lowered plasma insulin levels with a tendency to recovery in the post infusion period. Whereas PGA1 infusion resulted in a moderate but significant hypoglycaemia, the administration of E-series PGs always produced a hyperglycaemic effect. The interference of PGE1 on insulin response to classical insulinogogues (glucagon, aminophylline, and tolbutamide) was also investigated. The results of these experiments demonstrate that PGE1 exerts an inhibitory action on insulin response to all insulin releasing agents investigated. As regards the haemodynamic effects of PGs, PGE1 and PGE2 lowered the arterial blood pressure by about 20 percent, while PGA1 was almost completely ineffective. On the other hand, the lowering effect of PGE1 on circulating insulin levels remained unchanged in rats treated with reserpine. These findings thus rule out a sympathetic over-activity secondary to the lowered arterial blood pressure as the mechanism of action of PGE1. A possible direct interference with the adrenergic receptor system of the pancreatic islets was also ruled out since the inhibitory effect of PGE1 was not overcome by phentolamine pre-treatment.
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PMID:Reduction of circulating insulin levels during the infusion of different prostaglandins in the rat. 117 86

If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65% with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation. Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.
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PMID:Potentiation of insulin release by glucose in man. II. Role of the insulin response, and enhancement of stimuli other than glucose. 117 5

Insulin antagonism characterizes infection, but the mechanism is unknown. Previous studies have been performed during the acute catabolic stage of infection, and the resultant metabolic changes reflect this decreased food intake and weight loss. To delineate metabolic alterations due to infection itself, rats with pyelonephritis induced by tail-vein injection of 1 ml. of Streptococcus faecalis (10(9) bacteria per milliliter) were studied two weeks later during a period of near-normal weight gain and food intake. Fasting growth hormone concentrations (nanograms per milliliter) in the pyelonephritic rats were nearly five times normal (45.8 vs. 9.9). Intra-arterial glucose and insulin tolerance tests were impaired. Early glucose-induced insulin release was depressed. Fat pads from infected rats manifested higher basal lipolysis per cell. Glycerol-mediated gluconeogenesis by liver slices was decreased. This pathway was unaffected by insulin in infected rats but readily inhibited in control rats. The following metabolic parameters were similar in control and infected animals: (in vivo) fasting concentrations of plasma glucose, free fatty acids, triglycerides, total corticoids, creatinine, insulin, glucagon, molar ratios of insulin and glucagon, glucose and insulin responses to tolbutamide, and glucagon and free fatty acid suppression after glucose; (in vitro) glucose metabolism by muscle and fat, epinephrine- and theophylline-stimulated lipolysis and re-esterification by epididymal fat pads, fasting hepatic glycogen content, glucose production by liver slices with and without alanine. No plasma insulin antagonist was found in the infected rats. Metabolic alterations in infected rats can be demonstrated independently of the associated catabolism. Increased growth hormone secretion cannot explain all of these changes.
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PMID:Metabolic studies in the pyelonephritic rat. 117 60

The effect of low-dose somatostatin (2.5 mug/min i.v.) on blood sugar, insulin and GH levels (basal and after i.v. 1 mg glucagon) was studied in 7 normal and 10 acromegalic subjects. No changes in basal values were noted in normal subjects, whereas the insulin response to glucagon was partly inhibited and the glucose response enhanced. Basal blood glucose was likewise unaltered in the acromegalics. There was, however, a significant, though unrelated, fall in both insulin and GH. The insulin response to glucagon was inhibited to a greater degree than in normal subjects. It is clear, therefore, that somatostatin can inhibit the insulin response to glucagon, as well as that to the other stimuli for which data are given in the literature. Acromegalic subjects appear to be more sensitive to inhibition of insulin secretion by somatostatin, though no relation between this and the drug's parallel inhibition of GH secretion can be shown.
Acta Diabetol Lat
PMID:The effect of somatostatin on plasma insulin and growth hormone levels in basal conditions and after glucagon in normal and acromegalic subjects. 122 5

Plasma concentrations of insulin, growth hormone and glucagon were measured during an arginine test in obese women with normal (ON) or abnormal (OD) OGTT and in normal control subjects (N). Plasma insulin levels were higher than normal in both obese groups, while plasma growth hormone and glucagon levels were markedly reduced.
Acta Diabetol Lat
PMID:Glucagon, insulin and growth hormone response in obese women. 122 7

The acute effect of human growth hormone on glucagon--and tolbutamide--induced insulin release was investigated in 14 non-obese subjects with normal glucose tolerance. Sixty mn after an i.v. growth hormone infusion of 40 mug/kg per kg body weight, the insulin response to glucagon (10 subjects) as well as to tolbutamide (6 subjects) was significantly suppressed by about 35%, both if the insulin secretion was expressed as change in peak response (p less than 0.05 for both insulinogogues) or as per cent change of the integrated insulin area over 30 minutes (p less than 0.005 and p less than 0.05, respectively). A lesser reduction of glucagon-induced insulin secretion was observed also after smaller doses of growth hormone (10 and 20 mug/kg). The reduction of the insulin response was associated with a significantly smaller blood glucose fall following the glucagon and tolbutamide administration. These results support the hypothesis that growth hormone in vivo has an acute suppressive effect on insulin secretion, and show that this action is not limited to glucose-induced stimulation of the islets.
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PMID:Acute suppressive effect of human growth hormone on insulin release induced by glucagon and tolbutamide in man. 123 67

Subnormal growth hormone responses to both insulin-induced hypoglycemia and arginine infusion (peak response less than or equal to 5 ng/ml) were found in five male subjects (aged 10 to 14 years) with short stature but with normal interval growth rates and normal bone ages (in 4 cases). They demonstrated one or more normal GH responses to subsequent provocation by glucagon stimulation, tolbutamide-induced hypoglycemia, and repeat insulin and arginine testing following pretreatment with sex steroids. Two subjects had received exogensou GH therapy for six months prior to the subsequent assessment; each one failed to demonstrate the growth response characteristic of GH deficiency. These studies indicate the need for multiple provocative human GH testing to exclude children whose growth would not be enhanced by GH therapy despite a subnormal response to provocative tests with insulin and arginine.
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PMID:Provocative tests for growth hormone release. 125 12

In the classical model of isolated perfused rat pancreas four commonly used sulfonylureas--tolbutamide, glibenclamide, gliquidone and gliclazide--were investigated at therapeutical concentrations at three different glucose levels (with 0, 2.22 and 5 mmol/l glucose surrounding) and in the presence of a metabolic stimulus with glucose at 8.33 mmol/l. All the sulfonylureas stimulated the B-cell function. Tolbutamide, gliquidone and gliclazide produced a prompt biphasic hormone release while glibenclamide induced a delayed monophasic insulin secretion. In all cases the amount of insulin released depended on the metabolic condition. As the environmental glucose levels fell, the sulfonylureas' stimulatory effect on the B-cell function decreased. At the therapeutical concentrations we tested, no sulfonylurea influenced A-cell activity whether directly or indirectly via an insulin-mediated paracrine inhibition of glucagon release.
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PMID:Therapeutical concentrations of tolbutamide, glibenclamide, gliclazide and gliquidone at different glucose levels: in vitro effects on pancreatic A- and B-cell function. 128 21

The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary failure of oral hypoglycaemic agents in lean patients with type 2 diabetes mellitus: insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP. 131 98

To discriminate between true secondary failure (TF) and pseudo-secondary failure (PF) to oral hypoglycaemic agents, we studied 34 non-obese non-insulin-dependent diabetic patients who were being treated with these drugs. Nine were in good control (GC) with oral treatment, while 25 showed apparent SF. During a controlled hospital diet, fasting blood glucose remained persistently high in 15 of these patients (TF), while in the other 10 patients it clearly improved (PF). Fasting plasma glucose (FPG) and HbA1c were higher and body mass index (BMI) was lower in TF patients than in PF patients (P less than 0.01). C-peptide concentrations differed significantly among the three groups both in the fasting state (TF 0.25 +/- 0.02 nmol/l, PF 0.70 +/- 0.03 nmol/l, GC 0.74 +/- 0.03 nmol/l; P less than 0.0001) and 6 min after glucagon injection (TF 0.50 +/- 0.04 nmol/l, PF 1.02 +/- 0.06 nmol/l, GC 1.14 +/- 0.07 nmol/l; P less than 0.0001). C-peptide and plasma insulin curves obtained after a standard mixed meal also showed significant differences (P less than 0.001). In particular, there was a statistically significant difference between GC and PF versus TF (P less than 0.05), while there was no statistical difference between PF and GC. We conclude that some patients with apparent SF can improve their metabolic control if they strictly adhere to a correct diet (PF); a single measurement of basal C-peptide concentration or examination of the C-peptide and insulin responses to a meal are useful indicators for distinguishing patients with PF from those with TF to oral hypoglycaemic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Acta Diabetol 1992
PMID:A simple clinical approach to discriminate between "true" and "pseudo" secondary failure to oral hypoglycaemic agents. 152 Sep 1


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