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

The amount of neuroendocrine granules in microgranular cells of salivary glands were investigated in necropsies of 20 non-insulin dependent diabetics (NIDDM) and in 20 non-diabetic subjects with Grimelius and Fontana-Masson stainings. Granules in serous acini, and intercalated ducts were observed in both groups; however, a significant higher number of granules and microgranular cells were observed in NIDDM subjects as compared with non-diabetics. Both parotid and submaxillary glands were significantly heavier in NIDDM than in the non-diabetic group. These granules may be related to immunoreactive glucagon which has been found in submaxillary glands of rodents and might play a role in the pathogenesis of NIDDM. Further investigations should be performed to clarify whether these cells are the site of glucagon synthesis and also clarify the pathogenesis of NIDDM.
 ...
PMID:[Increase in neuroendocrine secretion granules in submaxillary and parotid glands in patients with non-insulin dependent diabetes mellitus]. 130 90

The effect of glycaemic control on the early morning plasma glucose rise, 'the dawn phenomenon', was assessed in two matching diabetic patient groups each comprising five NIDDM and two IDDM patients per group, who were otherwise considered to be in poor (HbA1 = 11.2 +/- 0.6%) or good (HbA1 = 7.6 +/- 0.2%) glycaemic control. Hourly plasma concentrations of glucose, insulin, glucagon, cortisol, and growth hormone were measured between 03.00 and 09.00 h. In all the poorly controlled diabetic patients the mean rise in plasma glucose between 06.00-08.00 and 03.00 h was greater than or equal to 1.0 mmol/l. In contrast, the plasma glucose increment was less than 1.0 mmol/l in the well controlled diabetics. The overnight mean insulin levels in the poor and well controlled patient groups were 19.3 +/- 0.5 and 25.0 +/- 0.6 mU/l (P less than 0.001) respectively. Glucagon, cortisol, and growth hormone levels in the early morning showed no significant differences between the two groups. The decline in plasma insulin from 03.00 to 08.00 h and mean cortisol level between 03.00 and 06.00 h were both significantly correlated with the increase in plasma glucose between 03.00 and 08.00 h. We concluded that an increase of 1.0 mmol/l or more in plasma glucose during the early morning is of clinical importance.
 ...
PMID:The dawn phenomenon and diabetes control in treated NIDDM and IDDM patients. 142 38

This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). 149 70

We investigated how different plasma glucose concentrations could significantly modify the C-peptide response to glucagon. Twenty poorly-controlled (HbA1c 10.2 +/- 1.5%) non insulin-dependent (NIDDM) subjects (body mass index 27 +/- 1.8), 2 treated with diet alone and 18 with oral hypoglycemic agents were studied. The first day glucagon (1 mg iv) was injected, patients being fasting and untreated. Mean plasma glucose levels were 11.4 +/- 1.2 mM. On a second non consecutive day, after an overnight fast, the same patients were connected to a closed-loop insulin infusion system (Betalike, Genoa), their blood glucose concentrations were stabilized within a normoglycemic range (5-5.5 mM) for 2 h and insulin infusion was stopped. The glucagon test was repeated 30 min later. Blood samples were taken 0, 6, 10, 20 min after glucagon injection. In the second test, basal, and 6, 10 and 20 min post-glucagon glucose levels were significantly lower (p less than 0.001); similarly C-peptide concentrations were significantly reduced both in basal conditions (0.55 +/- 0.04 vs 0.37 +/- 0.04 nM; p less than 0.001) and 6 (0.92 +/- 0.06 vs 0.6 +/- 0.06; p less than 0.001), 10 (0.79 +/- 0.06 vs 0.56 +/- 0.06; p less than 0.001) and 20 min (0.64 +/- 0.05 vs 0.44 +/- 0.04; p less than 0.001) after stimulation. The C-peptide secretion area showed the same trend (49.5 +/- 4.8 vs 32.1 +/- 5.8; p less than 0.001). In conclusion, our data confirms that blood glucose levels modulate the pancreatic insulin secretion; glycemic normalization significantly reduced both basal and post-glucagon C-peptide release.
 ...
PMID:The effect of various blood glucose levels on post-glucagon C-peptide secretion in type 2 (non insulin-dependent) diabetes. 156 91

Amylin, a peptide found in pancreatic amyloid deposits, may be involved in NIDDM. The effects of biosynthetic human amylin on multiple aspects of carbohydrate metabolism were studied in freshly isolated and cultured liver cells (rat hepatocytes and HepG2 cells). Acute exposure of culture liver cells to amylin had no effect on glucose incorporation into glycogen. Amylin directly reduced glucose oxidation through the hexose monophosphate shunt. The glycolytic pathway was unaffected. Amylin stimulated both glycogenolysis and gluconeogenesis. These effects were largest at amylin concentrations of 1-10 pM. Insulin partially inhibited both of these responses. Glucagon stimulated glycogenolysis and gluconeogenesis to a similar extent as amylin but required concentrations 100- to 500-fold as high. Thus, amylin, at physiologic concentrations, can impair some aspects of glucose use in liver cells and is also capable of directly stimulating glucose production, suggesting a possible involvement of amylin in the impaired glucose disposal and elevated hepatic glucose output of NIDDM.
 ...
PMID:In vitro effects of amylin on carbohydrate metabolism in liver cells. 162 73

To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone body production rates in hepatocytes from newly developed non-obese NIDDM model rats. NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2 or 5 days of age (STZ2, STZ5 respectively). After 10-15 weeks, ketone body production rates in hepatocytes isolated from these rats were compared with those from control rats as well as ketotic rats made by intravenous injection of streptozotocin into adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7 +/- 0.98, 14.9 +/- 0.72, 16.0 +/- 0.45, 22.8 +/- 2.32 nmole.palmitate/mg.prot/hr, respectively. These rates were stimulated by 1 microgram/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1 +/- 0.99, 18.6 +/- 1.36, 18.7 +/- 0.69 nmole.palmitate/mg.prot/hr, respectively), but not in ketotic rats (22.8 +/- 2.07 nmole.palmitate/mg.prot/hr). The similar effects were observed by 1 microgram/ml of epinephrine. The basal ketone body production rates were negatively correlated to both hepatic glycogen contents and plasma IRI levels. Considering these parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was between that in control and ketotic rats. These results indicate that the derangements of hepatic ketone body production are related to the severity of insulin deficiency and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated plasma ketone body levels in non-obese NIDDM.
 ...
PMID:Increased ketogenesis related to insulin deficiency in isolated hepatocytes from NIDDM model rats. 163 90

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.
 ...
PMID:The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy. 163 93

We used MK-912, a potent new selective alpha 2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective alpha 2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective alpha 2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P less than .01) and both systolic blood pressure (SBP) (P less than .01) and diastolic blood pressure (DBP) (P less than .05) after treatment with MK-912, but not after placebo. MK-912 caused a significant (P less than .05) although modest decrease of FPG that was associated with a small increase of fasting plasma insulin (P less than 0.01), C-peptide (P less than .05), and glucagon (P less than .01). FPG and hormone levels remained unchanged after placebo. MK-912 tended to increase the AIR (P = .06) and the C-peptide response (P = .07) to glucose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus. 168 87

The serum ketone response to glucagon was measured in 10 patients with IDDM and 37 with NIDDM. In both groups, serum 3-hydroxybutyrate increased significantly after intravenous injection of 1 mg glucagon. The difference between the serum level of 3-hydroxybutyrate at 30 min and basal level [delta 3-OHBA(30')] was 133 +/- 25 mumol/l in the patients with IDDM, 13 +/- 8 mumol/l in those with NIDDM treated by diet alone or with oral hypoglycemic agents and 23 +/- 13 mumol/l in those with NIDDM treated with insulin. The delta 3-OHBA(30') was significantly greater in IDDM patients than in both groups of NIDDM patients (P less than 0.001). The delta 3-OHBA(30') was greater than 87 mumol/l in eighty percent of IDDM patients, but smaller than 87 mumol/l in both groups of NIDDM patients. The delta 3-OHBA(30') was correlated with the difference between the plasma level of C-peptide at 6 min and basal level [delta CPR(6')] (r = -0.540, P less than 0.001). The delta 3-OHBA(30') was not correlated with fasting plasma levels of glucose, fructosamine or hemoglobin A1c. These observations show that measurement of the serum ketone response to glucagon is a useful marker of insulin dependency. In order to determine insulin dependency, the simultaneous measurement of concentrations of ketones and C-peptide is indicated during the glucagon stimulation test.
 ...
PMID:Serum ketone response to glucagon as a marker of insulin dependency in diabetics. 175 81

The efficacy and safety of gliclazide (Diamicron) were studied in 29 NIDDM patients (19 men and 10 women aged 25-68 years) who failed to improve with diet or with diet plus a sulfonylurea. All patients were overweight and had fasting blood glucose levels consistently above 150 mg/dl (8.24 mmol/l). After withdrawal of oral hypoglycemics where applicable, they received 40 mg Diamicron three times daily with meals. The dose was increased by 40-80 mg/day until optimum control was obtained or up to a maximum of 320 mg/day. Treatment lasted for 12 months. At the end of this period the mean fasting blood glucose level had fallen by 35% from 238 to 154 mg/dl and the mean 2-h postprandial blood glucose level had fallen by 28% from 237.7 to 195 mg/dl. The mean glycosylated hemoglobin level also fell by 30% from 10.10 to 7.02%, i.e. within the normal range. In addition, there was a 19% fall in triglyceride and a 10% fall in cholesterol levels, with no change in body weight. No changes were observed for serum insulin, C-peptide and glucagon levels, thyroid function tests, blood counts, liver and kidney function tests, uric acid, electrolytes, blood pressure or heart rate. No clinical or ECG abnormalities were observed in patients with or without cardiovascular disease. There were two presumptive hypoglycemic reactions, but these did not require treatment. Adverse effects were reported by 22 patients, including dizziness and light-headedness, diarrhea, nausea, palpitations and pruritus, but none required modification of Diamicron therapy. The results therefore show that Diamicron is safe, effective and well tolerated in suitably selected NIDDM patients.
 ...
PMID:Evaluation of the efficacy and safety of Diamicron in non-insulin-dependent diabetic patients. 179 70


1 2 3 4 5 6 7 8 9 10 Next >>