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)

Release of immature secretory granules rich in incompletely processed proinsulin has been proposed to explain the relative hyperproinsulinemia in type 2 diabetic and insulinoma patients because of a constant secretory drive resulting from hyperglycemia and autonomous secretion, respectively. To test this hypothesis, insulin secretion was stimulated by a combination of hyperglycemia (11 mmol/L clamp), intravenous (i.v.) tolbutamide (1 g), and i.v. glucagon (initial bolus 10 micrograms/kg body weight, maintenance infusion 2 micrograms/kg body weight per hour) for 3 h. Circulating IR-insulin and IR-C-peptide concentrations increased 89-fold and 14-fold over basal values, respectively, but IR-proinsulin concentrations increased only ninefold over basal values. Estimation of the amount of insulin secreted (based on deconvolution analysis of plasma C-peptide values) showed that approximately 76 +/- 21 U were secreted during the stimulation period. This amount is a significant proportion of pancreatic insulin content in normal humans. In molar terms, IR-proinsulin (integrated incremental response multiplied by metabolic clearance rate of proinsulin) relative to IR-C-peptide (= insulin) secretion (deconvolution analysis) was estimated to be equal or even lower than the known proportion in islets (0.22 +/- 0.05%). Thus, using a near-maximal stimulation of insulin secretion maintained long enough to cause release of amounts of insulin approaching the estimated pancreatic content, no preferential release of proinsulin was observed in normal humans. Therefore, the hyperproinsulinemia of type 2 diabetes and in insulinoma patients may be caused by additional defects in the proinsulin to insulin conversion process.
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PMID:Prolonged maximal stimulation of insulin secretion in healthy subjects does not provoke preferential release of proinsulin. 178 Mar 24

The paper is devoted to a study of the time course of lipid metabolism, analysis of glucose tolerance, change in indices of immunoreactive insulin, glucagon and C-peptide before the start of verapamil therapy and 6 mos. after it during monotherapy with this drug. These parameters were investigated in the blood serum using biochemical methods and radioimmunoassays. A marked antihypertensive effect was achieved in patients suffering from noninsulin dependent diabetes mellitus with concomitant essential hypertension of the 2nd degree. No negative effect on the pancreatic hormone secretion was noted. Lipid transport indices were improved.
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PMID:[Use of finoptin in patients with non-insulin-dependent diabetes mellitus with concomitant essential hypertension]. 178 2

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.
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PMID:Evaluation of the efficacy and safety of Diamicron in non-insulin-dependent diabetic patients. 179 70

Effective fuel metabolism is dependent on balances among exogenous and endogenous fuel availability, the glucagon/insulin ratio, and tissue insulin sensitivity. Diabetes mellitus results when imbalances occur. The resultant metabolic derangement is accompanied by abnormalities in carbohydrate, protein, and fat metabolism. The two most common forms of diabetes are insulin dependent (IDDM) and noninsulin dependent (NIDDM). IDDM is an autoimmune disease, characterized by insulinopenia and ketosis. NIDDM is related to impaired insulin secretion, defective tissue sensitivity, and abnormalities in glucose transporter proteins. This article describes normal fuel metabolism and traces the abnormal metabolic processes that lead to both IDDM and NIDDM.
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PMID:Normal fuel metabolism and alterations in diabetes mellitus. 184 Sep 66

In the present study a randomized cross-over design was used to determine the clinical usefulness of adding 16 g of beet fiber to the ordinary diet of non-insulin dependent diabetic (NIDDM) out-patients. In addition, fiber effects on the gastrointestinal hormone responses to a standardized test meal were evaluated. The study included five patients treated with diet alone and eight patients treated with diet and sulphonylurea (SU). Beet fiber supplementation resulted in a 10% reduction (P less than 0.01) of serum cholesterol in SU-treated patients. No differences were found for fasting blood glucose, glycated hemoglobin, serum triglycerides or body weight. In the diet-treated patients, fasting plasma somatostatin was elevated during the fiber period. However, postprandial responses of insulin, C-peptide, glucagon, gastric inhibitory peptide and somatostatin were not influenced by an increased fiber intake in any group. All patients experienced mild gastrointestinal discomfort during the fiber period. In view of the limited metabolic benefit of beet fiber treatment we conclude that there is little use for this type of dietary fiber in the routine treatment of patients with NIDDM.
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PMID:Metabolic effects and clinical value of beet fiber treatment in NIDDM patients. 185 Jun 91

The aim of the study was to assess, in patients with non insulin dependent diabetes mellitus (NIDDM), either with previous failure to sulphonylureas or insulin treated since the disease started, if the combination of gliclazide to insulin therapy might induce a reduction of daily insulin requirement. 30 caucasian type II patients used to self-monitoring (11 female, 19 male, mean age 55.78 +/- 8.07) with residual pancreatic function (glucagon induced C-peptide release = 1.01 +/- 0.70 microgram/ml) entered the study. 8 were excluded for non compliance or for high antiinsulin antibodies levels and 4 are still under study. Each patients was given, for 3 months, 240 mg of gliclazide in addition to usual daily dose of insulin. Data presented as mean +/- s.e.m. were analysed with analysis of variance (p less than 0.05). Mean initial values of main parameters were as follows: glycaemia 192.7 +/- 33.1 mg/100 ml, insulinaemia 9.5 +/- 4.5 microUI/ml, daily insulin requirements 33.11 +/- 10.47 U/d, HbA1 C 7.5 +/- 1.7%. Total cholesterol 240.1 +/- 52.2 mg/10 ml, triglycerides 120.6 +/- 60.3 mg/100 ml. After 3 months treatment significant reduction in mean daily insulin requirements (20.78 +/- 16.15 U/d) was observed. In 13 patients (72.2%) while keeping good metabolic control (HbA1 C 7.46 +/- 1.63), insulin therapy was reduced (9 patients) or even stopped (4 patients). In the other 5, insulin was maintained or slightly increased. The increase in glucagon induced C-peptide release (1.41 +/- 0.99 micrograms/ml) did not reach significance, while glycaemia and insulinaemia were not changed (196.0 +/- 34.1 mg/100 ml, 11.02 +/- 5.05 microUI/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Beneficial effects of added glicazide in patients with type II diabetes mellitus treated with insulin]. 186 20

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by fasting hyperglycemia associated with defects in the pancreatic islet, the liver, and the peripheral tissues, which together comprise a feedback loop responsible for maintenance of glucose homeostasis. This review focuses on the key role of the endocrine pancreas alpha and beta cells to coordinate glucose output from the liver with glucose utilization. The basal rate of hepatic glucose utilization. The basal rate of hepatic glucose production is elevated in subjects with NIDDM, and this is positively correlated with the degree of fasting hyperglycemia. This increased rate of glucose release by the liver results from impaired hepatic sensitivity to insulin, reduced insulin secretion, and increased glucagon secretion. Though basal immunoreactive insulin levels in patients with NIDDM may appear normal when compared with healthy individuals, islet function testing at matched glucose levels reveals impairments of basal, steady-state, and stimulated insulin secretion due to a reduction in beta-cell secretory capacity and a reduced ability of glucose to suppress glucagon. The degree of impaired beta-cell responsiveness to glucose is closely related to the degree of fasting hyperglycemia but in a curvilinear fashion. The efficiency of glucose uptake by the peripheral tissues is also impaired due to a combination of decreased insulin secretion and defective cellular insulin action. This impairment becomes more important to the hyperglycemia as the islet alpha- and beta-cell function declines. Therapeutic interventions, to be effective, must reduce hepatic glucose production either by improving islet dysfunction and raising plasma insulin levels, or improving the effectiveness of insulin on the liver. Both result in a decline in the fasting glucose levels regardless of the cause of hyperglycemia. We conclude that NIDDM is characterized by a steady-state re-regulation of plasma glucose concentration at an elevated level in which islet dysfunction plays a necessary role. Treatment should be based on this physiologic understanding.
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PMID:Mechanisms for hyperglycemia in type II diabetes mellitus: therapeutic implications for sulfonylurea treatment--an update. 187 10

To define the spontaneous diurnal variations in glucose regulation during fasting in noninsulin-dependent diabetes (NIDDM), we measured circulating levels of glucose, insulin, C-peptide, GH, cortisol, and glucagon at 15-min intervals in 11 patients with untreated diabetes and 7 matched control subjects studied during a 24-h period. The rates of insulin secretion were derived from the concentrations of C-peptide by deconvolution using a two-compartment mathematical model for C-peptide distribution and metabolism. In both groups of subjects, despite continued fasting, glucose levels stopped declining in the evening and subsequently rose throughout the night to reach a morning maximum. Elevated levels persisted until noon. The morning glucose maximum corresponded to a relative increase of 23.8 +/- 5.5% above the evening nadir in NIDDM patients and 13.2 +/- 4.6% in nondiabetic subjects (P less than 0.05). In NIDDM patients, insulin levels and insulin secretion rates did not parallel the nocturnal glucose changes. In contrast, in control subjects, this nocturnal glucose rise coincided with a similar increase in insulin secretion rates. Cortisol concentrations in patients with NIDDM were higher than those in control subjects throughout the study period (P less than 0.001) and rose earlier in the evening than in control subjects, thus failing to demonstrate the normal nocturnal suppression. In both groups of subjects, the nighttime glucose elevation was temporally and quantitatively correlated with the circadian cortisol rise. GH secretion was increased in the evening and nighttime periods compared to the daytime values, and in NIDDM patients, but not in control subjects, the size of the morning glucose elevation was directly related to the magnitude of this increase in GH secretion (r = 0.88; P less than 0.01). Glucagon concentrations were similar in both groups of subjects and remained essentially constant throughout the study period. We hypothesize that the nocturnal glucose rise that occurs during fasting represents a normal diurnal variation in the set-point of glucose regulation amplified by counterregulatory mechanisms activated by the fasting condition.
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PMID:Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes. 199 13

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration. In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed that arginine stimulated the secretion of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an insulinotropic hormone. The elevated levels of immunoreactive GLP-1 in diabetics in the fasting state were mainly due to an increased concentration of major proglucagon fragment.
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PMID:Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. 199 27

To assess the effect of metyrapone on the early morning plasma glucose (PG) rise, seven NIDDM patients were studied from 2400 to 0900 h on two separate occasions one week apart. During the control study nights, patients received conventional therapy only (diet plus sulphonylurea) whereas on treatment nights, patients received in addition 30 mg/kg metyrapone orally at 2400 h. The plasma glucose (PG) levels from 0530 to 0900 h were significantly higher during the control night than the corresponding values following metyrapone. The control mean PG concentrations increased continuously from a nadir 8.4 +/- 1.1 mmol/l at 0400 h to a maximum of 9.4 +/- 1.1 mmol/l at 0800 h (p less than 0.01). In contrast following metyrapone administration a continuous decline in the PG concentration was noted from 2400 to 0800 h. The plasma glucose levels fell from 9.0 +/- 1.2 at 0400 h to 7.7 +/- 1.0 mmol/l at 0800 h (p less than 0.05). The mean overnight cortisol levels were 167.2 +/- 13.2 and 55.9 +/- 6.4 nmol/l (p less than 0.001) during the control and treatment studies, respectively. The cortisol levels were significantly higher during the control study at all time points from 0400 to 0900 h. No significant changes in insulin, C-peptide, glucagon, GH or catecholamine levels were observed between the two study periods. We conclude that the physiologic early morning rise in plasma cortisol possibly contributes to the pathogenesis of the dawn phenomenon in NIDDM patients.
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PMID:Early morning hyperglycaemia "dawn phenomenon" in non-insulin dependent diabetes mellitus (NIDDM): effects of cortisol suppression by metyrapone. 213 91


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