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)

To ascertain whether the dawn phenomenon occurs in nondiabetic individuals and, if so, whether it is due to an increase in glucose production or a decrease in glucose utilization, we determined plasma concentrations of glucose, insulin, C-peptide, and counterregulatory hormones, as well as rates of glucose production, glucose utilization, and insulin secretion at one-half-hourly intervals between 1:00 and 9:00 a.m. in eight normal volunteers. After 5:30 a.m., plasma glucose, insulin, and C-peptide concentrations all increased significantly; rates of glucose production, glucose utilization, and insulin secretion also increased (all P less than 0.05). Plasma cortisol, epinephrine, and norepinephrine increased significantly from nocturnal nadirs between 4:00 and 6:30 a.m. Plasma growth hormone, which had increased episodically between 1:00 and 4:30 a.m., decreased thereafter nearly 50% (P less than 0.05). Plasma glucagon did not change significantly throughout the period of observation. These results indicate that a dawn-like phenomenon, initiated by an increase in glucose production, occurs in nondiabetic individuals. Thus, early morning increases in plasma glucose concentrations and insulin requirements observed in IDDM and NIDDM may be an exaggeration of a physiologic circadian variation in hepatic insulin sensitivity induced by antecedent changes in catecholamine and/or growth hormone secretion.
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PMID:Demonstration of a dawn phenomenon in normal human volunteers. 638 30

A description is given of the electron microscopic-morphometric findings obtained for the islets of Langerhans of the pancreas and for the glucagon-producing A cells of one patient suffering from longstanding insulin-dependent diabetes mellitus (IDDM, type I diabetes), two patients with longstanding insulin-independent diabetes mellitus (NIDDM, type II diabetes), and one non-diabetic. A morphometric determination of the volume densities of the vascular connective tissue and the various endocrine cells per islet tissue and organelles/ultrastructures per A cell was made, and the diameters of the A-granules were measured. So far, no such studies have been made for human diabetes mellitus, and only a few are available for humans with sound metabolism. In general, the qualitative and, particularly, the quantitative electron microscopic results found for the IDDM patient show greater and clearer deviation from the control with normal metabolism than the findings obtained for the NIDDM patients. As regards the cellular composition of the pancreatic islets and changes caused by diabetes mellitus, the morphometric values obtained from electron micrographs are in essential agreement with comparable findings reported in the literature for light microscopic-histochemical and -immunohistochemical morphometry. The patient with insulin-dependent diabetes has a higher proportion of vascular connective tissue in the pancreatic islets than the non-diabetic. This increase is both relative and absolute and is primarily connected with the loss of B cells in this type of diabetes. In the IDDM patient, A cells were found in the islets but also scattered as single cells in the exocrine tissue and in the walls of pancreatic ductules. The ultrastructural composition of the A cells varies within wide limits even in persons with sound metabolism. Diabetes mellitus does not cause major qualitative alterations in the A cells. The A cells of the IDDM patient contained a remarkable number of nuclei and rarely showed A-granule crinophagia. The casuistic electron microscopic findings, most of which have been obtained for the first time, are discussed. Nothing can be said at this stage about the general applicability of the findings. The morphometric results obtained for the A cells can be interpreted as indicating increased metabolism with heightened glucagon synthesis and secretion in the case of the insulin-dependent diabetic and, to a lesser extent, in the NIDDM patients. This interpretation would support the assumption of a normally existing mutual local paracrine regulation of the A and B cells which stems from close topographical relations (contact, gap junctions).
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PMID:[Electron microscopic findings in A-cells of the islands of Langerhans in diabetes mellitus]. 639 63

To ascertain whether the ability of glucose to influence the pancreatic islets response to a nonglucose stimulus is normal in type II diabetics, we have evaluated the modulating effect (Md) of the plasma glucose level (PG) on the acute insulin response (IRI) and glucagon response (IRG) to intravenous arginine in noninsulin-dependent diabetics (NIDDM) and nondiabetics (ND). MdIRI or MdIRG is the change in the hormonal response to arginine resulting from changes in plasma glucose level divided by the change in plasma glucose. Md has been determined over two ranges of PG: between normal fasting PG (level I) and mild hyperglycemia (approximately 160 mg/dl, level II) and between mild hyperglycemia and marked hyperglycemia (approximately 350 mg/dl, level III). Increases in PG augmented the IRI response in both groups, but the degree of augmentation was impaired in the NIDDM group. MDIRI for ND and NIDDM between levels I and II were 20 +/- 3 and 1.9 +/- 0.6, respectively, and between levels II and III were 23 +/- 5 and 2.3 +/- 0.5, respectively (P less than 0.01). MdIRI correlated with fasting PG in ND and NIDDM. Changes in PG resulted in equivalent changes in the IRG response to arginine in both groups. MdIRG for level I to II was -6.2 +/- 1.0 and -6.0 +/- 1.2, and for level II and III was -0.9 +/- 0.4 and -1.2 +/- 0.5 in ND and NIDDM, respectively. The impairment of MDIRI and its relationship to fasting PG in NIDDM support the hypothesis that fasting hyperglycemia may be, in part, a compensatory mechanism for maintaining beta-cell response to nonglucose stimuli, thereby maintaining basal insulin levels. MdIRG was normal in NIDDM when evaluated at comparable glucose levels in the ND and NIDDM groups.
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PMID:Glucose modulation of insulin and glucagon secretion in nondiabetic and diabetic man. 675 65

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

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

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

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

Glucagon-like peptide-1 (GLP-1) is a hormone derived from the preproglucagon molecule that is secreted by intestinal L cells and stimulates insulin secretion from beta cells. The GLP-1 receptor is a candidate gene for diabetes mellitus, as mutations may induce the impaired insulin response that is a characteristic feature of NIDDM. To study the relationship between the GLP-1 receptor gene and NIDDM, linkage of a microsatellite polymorphism flanking the GLP-1 receptor gene with diabetes was investigated in three Caucasian families with MODY and in the nuclear families of 12 NIDDM probands. A cumulative LOD score -8.50 excludes linkage in these MODY pedigrees. A LOD score of -1.24 in the NIDDM nuclear pedigrees makes linkage improbable. Mutations in or near the GLP-1 receptor gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but we cannot exclude a role for this locus in a polygenic model or a major role in some pedigrees.
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PMID:Non-linkage of the glucagon-like peptide 1 receptor gene with maturity onset diabetes of the young. 795 45

Glucagon-like peptide-1 (GLP-1) stimulate glucose dependent insulin secretion from beta-cells. Human cDNA and the gene of the receptor for the GLP-1 was isolated. Two polymorphic simple tandem repeats were found in the gene. Using these markers, role of GLP-1 receptor mutations in the pathogenesis of NIDDM was studied. No association was found between the marker alleles and NIDDM in African American or in Japanese. Linkage was rejected between the GLP-1 receptor gene and NIDDM in Caucasian late-onset NIDDM families and in French MODY families. Mutations in the GLP-1 receptor gene do not appear to be major genetic determinants of NIDDM. Further studies are required to exclude the minor role of the gene in a fraction of NIDDM patients.
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PMID:[Human glucagon-like peptide-1 receptor gene in NIDDM]. 798 6

To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2-4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM.
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PMID:Natural history of B-cell dysfunction in spontaneously diabetic Chinese hamsters. 798 44


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