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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the precise significance of pancreatic A-cell hypersecretion in the pathogenesis of diabetes mellitus, the change in the immunoreactive glucagon (IRG) response to intravenous arginine was studied in both nonobese, hypoinsulinemic non-insulin-dependent (NIDDM) and insulin-dependent diabetic (IDDM) subjects whose blood glucose responses and plasma immunoreactive insulin (IRI) simulated those of healthy subjects with the aid of the artificial beta-cell system that we originally developed. In both five NIDDM and five IDDM subjects, blood glucose responses and plasma IRI after arginine challenges were made equivalent to those seen in healthy subjects by infusing insulin in response to blood glucose, revealing that previously exaggerated IRG responses were made completely similar to the responses in healthy subjects. In summary, these results clearly demonstrate that the exaggerated response of A-cell secretion against arginine challenges in insulin-deficient diabetics is secondary to insulin lack, and the perfect normalization of its response is achieved only when both plasma insulin concentration and glycemic control simulate those of healthy subjects.
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PMID:Perfect normalization of excessive glucagon responses to intravenous arginine in human diabetes mellitus with the artificial beta-cell. 700 90

Primary diabetes mellitus is usually subdivided into the types JOD and MOD. In MOD different insulin secretion patterns may be found. The authors have checked the frequency of the different patterns of disturbed insulin secretion in a number of 130 indiscriminate MOD-patients. It was investigated to what extent the insulin values correlated with the fasting blood glucose level. The results show that in fasting blood sugar values up to 140 mg/dl a highly different behaviour of the insulin secretion is present. In this range different etiopathogenetic clinical pictures certainly exist. With increasing blood sugar values a reduction of the insulin secretion is to be expected with increasing probability. In 24% of the patients an increase of the insulin levels in the blood after administration of glucose was missing altogether. In 96% of the patients with MOD additional stimulation by glucagon led to a significant increase of the insulin levels in the blood. As concerns treatment a still existing own insulin secretion of the patients should be assumed in those cases where the blood sugar values are only slightly elevated. It is not possible to derive the necessity of an additional treatment with sulfonylureas from the fasting blood sugar level or from the insulin values alone.
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PMID:[Insulin secretion in maturity-onset- diabetes--indications for etiopathogenesis and therapy]. 701

The effect of weight loss and caloric restriction on plasma glucose concentrations and insulin and glucagon secretion in response to oral and iv glucose and arginine infusions was examined in 8 subjects with type II diabetes mellitus of greater than 5 yr duration (long term diabetes). The findings of this study were compared to previous results in 10 subjects with similar degrees of obesity and fasting hyperglycemia but diabetes of less than 2 yr duration (recent-onset diabetes; fasting plasma glucose, 267 +/- 16.5 mg/dl in long term diabetics and 259 +/- 8.0 mg/dl in recent onset diabetics) and to a control group of 8 similarly obese but nondiabetic subjects. Both diabetic groups had impaired insulin responses on initial and final tests compared to control subjects. Response to dietary therapy was significantly poorer in the diabetics of longer duration (final fasting plasma glucose, 175 +/- 18.9 mg/dl in long term vs. 119 +/- 6.2 mg/dl in recent-onset subjects; P less than 0.01) despite a similar degree of weight loss and duration of diet therapy in the 2 groups. This difference in glucose tolerance occurred despite similar final insulin and glucagon responses in the diabetic groups. Subjects with type II diabetes of long duration appear to have a relatively greater degree of insulin resistance than subjects with more recent onset of the disease.
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PMID:Diminished effect of caloric restriction on control of hyperglycemia with increasing known duration of type II diabetes mellitus. 702 80

Because the supplementation of pyridoxine (vitamin B6) improves the glucose tolerance in gestational diabetes and adult onset diabetes, pyridoxine deficiency has been considered to be one of the factors that cause diabetes mellitus. We produced pyridoxine deficient rats by giving pyridoxine-free food with deoxypyridoxine which competitively the activity of pyridoxal phosphate. In these pyridoxine deficient rats plasma insulin during the glucose tolerance test was significantly low as compared with controls. In vitro experiments of pancreas perfusion showed that secretion of insulin and glucagon was impaired in the pyridoxine deficiency. Since the restriction of diet-calorie caused a decrease in arginine-induced secretion of insulin and glucagon from the isolated pancreas, the impairment of the endocrine pancreas may depend on malnutrition. Pyridoxine deficiency is surely one of the factors that impair the endocrine pancreas by multifactorial derangement of metabolism besides the tryptophan-nicotinic acid pathway.
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PMID:The endocrine pancreas in pyridoxine deficient rats. 703 87

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor. Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. When transfected stably into fibroblast CHL-cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under stimulation with human GIP-1-42 (EC50 = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2 x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. In transfected CHL cells, GIP-1-42 did not increase intracellular calcium. Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.
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PMID:Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. 758 26

From pluripotent pancreatic rat islet tumor tissue we have previously reported the isolation of stable transplantable glucagonoma tumor phenotypes in rats characterized by acute onset of anorexia. We now report that these tumors also cause severe adipsia. Food and water intake is reduced by more than 95% and is immediately cured upon tumor removal. Four anorectic tumor lines were all characterized as glucagonomas with high levels of proglucagon mRNA, and of two tested both were associated with highly elevated plasma levels of glucagon as well as of Glp-1(7-36amide) in the host rat. This fetal processing pattern of proglucagon may be indirectly linked to the anorectic phenotype, since we have now isolated a non-anorectic glucagonoma with similar levels of proglucagon mRNA. Lack of anorexia/adipsia in SV-40-T-antigen driven glucagonomas in transgenic mice with similar fetal processing as reported by other suggests that our tumors produce a novel anorectic substance. This factor ranges among the most potent of its kind as a peripheral mediator involved in appetite and thirst regulation. In summary, the glucagonomas provide an interesting tool with which to study the nature of severe anorexia as well as adipsia, and the identification of the active substance(s) may provide novel therapeutics for the treatment of obesity-related disorders such as NIDDM.
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PMID:Transplantable glucagonomas derived from pluripotent rat islet tumor tissue cause severe anorexia and adipsia. 765 79

Cats are one of the few species that develop a form of diabetes mellitus that is clinically and histologically analogous to human type 2 diabetes mellitus. Figure 9 summarizes the etiologic factors thought to be involved in the development of feline and human type 2 diabetes. The main metabolic characteristics of type 2 diabetes mellitus are impaired insulin secretion and resistance to the action of insulin in its target tissues. Impaired beta cell function occurs before histologic changes become evident. The characteristic histologic finding in cats with type 2 diabetes is deposition of amyloid in pancreatic islets. Amyloid deposition occurs before the onset of clinical signs, but does not seem to be the primary defect. Pancreatic amyloid is derived form the recently discovered pancreatic hormone amylin. Amylin is synthesized in pancreatic beta cells, and is co-stored and co-secreted with insulin. Amylin has been postulated to be involved in the pathogenesis of feline diabetes mellitus both through its metabolic effects, which include inhibition of insulin secretion and induction of insulin resistance, and via progressive amyloid deposition and beta cell degeneration. Increased amylin concentration has been documented intracellularly in cats with impaired glucose tolerance and in the plasma of diabetic cats, and supports the hypothesis that amylin is involved in the pathogenesis of type 2 diabetes. Obesity is a common finding in diabetic felines and is a contributing factor to the insulin resistance present in type 2 diabetes. Clinical signs of diabetes develop once total insulin secretion decreases to 20% to 25% of normal levels. Many diabetic cats have been treated successfully with oral hypoglycemics, but 50% to 70% of diabetic cats are insulin dependent. Based on histologic evidence, this is the result of extensive amyloid deposition and subsequent beta cell degeneration, rather than autoimmune destruction of pancreatic beta cells associated with type 1 diabetes. Alternative ways of treating type 2 diabetes currently are being investigated. Amylin antagonists recently have been proposed as a novel treatment to reverse the deleterious effects of excessive amylin concentrations. The gastrointestinal hormone glucagon-like peptide-1 may also prove useful in treating diabetic cats, because of its stimulatory effect on insulin secretion and synthesis, and the absence of significant hypoglycemic effect.
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PMID:Pathogenesis of feline diabetes mellitus. 766 May 30

In order to determine whether there is any relationship between pancreatic reserve and the insulin dose required for achieving a good metabolic control in type 2 diabetic patients with secondary failure to oral hypoglycaemic agents, fasting and post-glucagon C-peptide were determined in thirty-nine type 2 diabetic patients with secondary failure to sulphonylureas and hyperglycaemia < 250 mg/dl who attended an outpatient clinic. M-value was calculated in patients performing self-monitoring of blood glucose. Otherwise, pre- and post-prandial glycaemias were measured bi-weekly as outpatients. HbA1c and fructosamine were assessed monthly. A patient was considered well controlled when he or she fulfilled all the requirements of the European NIDDM Policy Group and the insulin dose necessary for these goals was correlated to the pancreatic reserve. There were two drop-outs. Thirty-five out of the thirty-seven patients complied with the objectives in an average time of 3.14 +/- 1.93 months. At the beginning of the study mean HbA1c was 8.01 +/- 1.40% and fructosamine 343.81 +/- 59.05 micromol/l, whereas at the end of the study the values were 6.91 +/- 0.94% and 291.89 +/- 38.59 micromol/l, respectively (both p < 0.001). Body weight increased from 68.95 +/- 12.40 to 69.44 +/- 12.54 kg (n.s.), while hypoglycaemic events decreased from 1.70 +/- 2.37 to 0.88 +/- 1.33 events/week (p < 0.05). To attain all the objectives, 19.03 +/- 5.98 i.u. (0.28 +/- 0.08 i.u./kg) of insulin were required. Basal and post-glucagon C-peptide were 1.97 +/- 1.24 and 3.29 +/- 1.85 ng/ml, respectively, with an increase of 1.32 +/- 0.78 ng/ml. All these values inversely correlated with insulin dose, especially the increase during the test (r = -0.652 with i.u./kg and r = -0.599 with i.u., both p < 0.01). In conclusion, C-peptide test is a good indicator of the insulin dose required for achieving the aims of metabolic control in type 2 diabetic patients.
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PMID:Pancreatic reserve and insulin dose in type 2 diabetic patients. 771 86

Non-insulin-dependent diabetes mellitus (NIDDM) affects about 5% of the world population. The disease presents a polygenic mode of inheritance, but mechanisms and genes involved in late-onset NIDDM are largely unknown. We report the association of a single heterozygous Gly to Ser missense mutation in the glucagon receptor gene with late-onset NIDDM. This mutation was highly associated with NIDDM in a pooled set of French and Sardinian patients (chi 2 = 14.4, P = 0.0001) and showed some evidence for linkage to diabetes in 18 sibships from 9 French pedigrees (chi 2 = 6.63, P < 0.01). Receptor binding studies using cultured cells expressing the Gly40Ser mutation demonstrate that this mutation results in a receptor which binds glucagon with a three-fold lower affinity compared to the wild type receptor.
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PMID:A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. 777 93

Glucagon-like peptide-I(GLP-I), encoded by the glucagon gene and released from the gut in response to nutrients, is a potent stimulator of glucose-induced insulin secretion. In human subjects GLP-I exerts its physiological effect as an incretin. The incretin effect of GLP-I is preserved in patients with Type II diabetes mellitus (NIDDM), suggesting that GLP-I receptor agonist can be used therapeutically in this group of patients. In these studies we addressed the question of whether GLP-I has broader actions in human physiology. To investigate this issue we examined the tissue distribution of GLP-I receptor using RNAse protection assay in order to avoid the cross-reactivities with structurally related receptors and to increase the sensitivity of detection. The riboprobe was synthesized from the human pancreatic GLP-I receptor cDNA and used in hybridization experiments with total RNA isolated from different human tissues. In addition to the pancreas, we found expression of GLP-I receptor mRNA in lung, brain, kidney, stomach and heart. Peripheral tissues which are the major sites of glucose turnover, such as liver, skeletal muscle and adipose did not express the pancreatic form of the GLP-I receptor. We also cloned and sequenced GLP-I receptor cDNA from human brain and heart. The deduced amino acid sequences are the same as the sequence found in the pancreas. These results indicate that GLP-I might have effects beyond the pancreas, including the cardiovascular and central nervous systems where a receptor with the same ligand binding specificity is found.
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PMID:Tissue-specific expression of the human receptor for glucagon-like peptide-I: brain, heart and pancreatic forms have the same deduced amino acid sequences. 784 4


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