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)

In order to assess the adrenergic contribution to hypoglycemic glucose counterregulation in type I diabetes mellitus and to determine whether the adrenergic contribution is mediated through beta 1- or beta 2-adrenergic receptors, hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 x min) for 60 min in 11 insulin-dependent diabetic patients (IDDM), 5 with normal plasma glucagon responses and 6 with blunted responses, and also in 7 age-weight-matched nondiabetic subjects. Rates of plasma glucose decrease and postnadir increase, as well as plasma concentrations of free insulin and of counterregulatory hormones, were measured when insulin was infused alone, and when insulin was infused along with propranolol (a beta 1- and beta 2-adrenergic receptor antagonist) or metoprolol (a selective beta 1-antagonist). Postnadir plasma glucose recovery was decreased in IDDM with blunted plasma glucagon responses (21 +/- 0.8 mumol x L-1 x min-1, P less than 0.001), but was normal in patients with normal plasma glucagon responses (30 +/- 0.4 versus 33 +/- 0.5 mumol x L-1 x min-1 in nondiabetic subjects, P = NS). Postnadir plasma glucose recovery was not affected by either propranolol or metoprolol in normal subjects and in IDDM with normal glucagon responses. However, in IDDM with blunted plasma glucagon responses, postnadir plasma glucose recovery was further decreased by propranolol (14 +/- 0.6 mumol x L-1 x min-1, P less than 0.01), but was unaffected by metoprolol (22 +/- 0.9 mumol x L-1 x min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The adrenergic contribution to glucose counterregulation in type I diabetes mellitus. Dependency on A-cell function and mediation through beta 2-adrenergic receptors. 631 52

The short-term effect of the glucose-controlled insulin infusion system (GCIIS) Biostator on metabolic and hormonal responses to a 2 h glucose infusion (0.33 g/kg body weight glucose i.v. followed by an infusion of 12 mg/kg/min) was studied in 8 insulin-dependent diabetic patients (IDDM). Normalization of glucose tolerance by means of GCIIS was associated with significant improvement of lipid metabolism in IDDM. Endogenous insulin secretion (C-peptide) was not altered significantly under the experimental conditions. The results demonstrate that immunoreactive glucagon response to intravenous glucose infusion was restored by treatment with GCIIS in IDDM irrespective of no prolonged duration of normoglycemia. The results provide further support that abnormal glucagon response in some IDDM is secondary to insulin deficiency.
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PMID:Short-term of the artificial beta-cell (Biostator) on pancreatic glucagon response in insulin-dependent diabetic (IDDM). 638 51

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

The pathophysiology of beta cell failure in IDDM has not been well documented. Islet cell responsiveness (C-peptide and glucagon) to oral glucose (OGTT), intravenous glucose (IVGTT), and arginine infusion was studied sequentially in a 24-yr-old nonobese patient with IDDM in prolonged remission interrupted by an episode of diabetic ketoacidosis and followed by a second transient (6 mo) partial recovery of beta cell function. The earliest abnormality in glucose tolerance was demonstrated with the IVGTT (K = 0.77) although OGTT (F, 101: 1/2 h, 177; 7 h, 211; 1 1 h, 144; and 2 h, 111 mg/dl) and glucagon responses to glucose and arginine were normal. With the development of abnormal OGTT, glucagon failed to suppress with hyperglycemia although basal levels were not elevated. With the development of frank clinical diabetes, C-peptide did not respond to oral or i.v. glucose although stimulation in response to arginine infusion was still possible. Basal glucagon concentrations were now elevated. Thus, the failing beta cell shows a progressive deterioration in its responsiveness to various secretagogues in a sequential manner (i.v. glucose followed by oral glucose and then i.v. arginine). Abnormalities in glucagon secretion can be demonstrated early in the development of abnormal oral glucose tolerance. With more precise elucidation of the etiology of diabetes, it may be possible to intervene therapeutically in diabetic individuals who experience a remission in order to prevent further deterioration in beta cell function.
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PMID:Pathophysiology of beta cell failure after prolonged remission of insulin-dependent diabetes mellitus (IDDM). 642 54

The spontaneously diabetic BB Wistar rat shows many characteristics analogous to human insulin-dependent diabetes (IDDM). These include inappropriately normal immunoreactive glucagon in the presence of hyperglycemia, absolute hyperglucagonemia with severe ketosis, and hyperresponsiveness to exogenous arginine in vivo. We used an in situ pancreas preparation to further study portal vein glucagon responses to intravenous arginine. In normal rats, magnitude of response was correlated with prestimulation levels. Basal levels were significantly increased in hyperglycemic diabetics compared to controls, but responses to arginine were attenuated in both absolute and relative terms. Comparisons of responses with poor and good prior diabetes control showed no significant differences. Thus, a further anomaly of glucagon secretion has been identified in these rats.
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PMID:Arginine-induced glucagon secretion in the spontaneously diabetic BB Wistar rat. 684 59

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

To explore humoral immunity in insulin-dependent diabetic (IDDM) patients, we studied insulin release from isolated mouse islets stimulated by glucose + theophylline after incubation with the sera of these patients and complement. Eleven of 21 IDDM sera suppressed the stimulated insulin release while the arginine-stimulated glucagon release remained unchanged. Morphologic evidence and the trypan-blue exclusion test suggested that the suppression of insulin release was due to a cytotoxic effect of the sera. No beta-cell inhibition of morphologic damage was detectable in the presence of sera from 30 healthy subjects, 8 non-insulin-dependent diabetic patients, and 5 nondiabetic patients with autoimmune diseases. Beta-cell inhibition by IDDM sera was not observed when complement was omitted. After serum fractionation, the cytotoxic potency of IDDM sera was located in the immunoglobulin G fraction. Using human islets, insulin release was suppressed by 3 of 6 IDDM sera. Complement-dependent cytotoxicity was found in 1 of 5 recent-onset IDDM patients and 11 of 16 IDDM patients with autoimmune phenomena. It was associated in all cases with the presence of islet cell antibodies as detected by immunofluorescence, and with the presence of circulating lymphocytes which suppressed insulin release in vitro. Complement-fixing antibodies may contribute to the selective beta-cell damage in IDDM.
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PMID:Complement-fixing Islet cell antibodies from some diabetic patients alter insulin release in vitro. 703 Aug 31

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.
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PMID:Relationship of glycosylated haemoglobin to C-peptide secretory status and antibody binding of insulin in insulin-dependent diabetes. 703 Aug 98

Glucagon (1-1.5 mg) was administrated iv as a bolus dose to healthy individuals (n = 7), patients with GH deficiency (n = 14), and patients with insulin-dependent diabetes mellitus (IDDM; n = 6). Thereafter, blood samples for determination of serum glucose, insulin, insulin-like growth factor-binding protein-1 (IGFBP-1), GH, and insulin-like growth factor-I (IGF-I) concentrations were collected for 180 min. IGFBP-1 concentrations increased significantly in response to glucagon, with maximal values observed at 90 min [in healthy subjects from 36 +/- 6 to 58 +/- 10 micrograms/L (P < 0.05), in GH-deficient patients from 36 +/- 4 to 54 +/- 6 micrograms/L (P < 0.001), and in IDDM patients from 115 +/- 18 to 167 +/- 27 micrograms/L (P < 0.05)]. The IGFBP-1 elevation was delayed in relation to the glucagon-induced increase in glucose and insulin concentrations. When the groups were combined, the individual IGFBP-1 peak value observed at 90 min was inversely correlated to the individual peak value of insulin observed at 15-30 min (r = -0.743; P < 0.001). In GH-deficient patients, serum GH concentrations remained undetectable (< 0.2 micrograms/L), and IGF-I concentrations were unchanged after the glucagon injection. In healthy subjects and IDDM patients, mean GH levels did not change significantly, whereas mean IGF-I concentrations decreased slightly at 30 min. In conclusion, glucagon increased serum IGFBP-1 concentrations in spite of increases in glucose and insulin. These results suggest that glucagon is a stimulator of IGFBP-1.
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PMID:Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus. 752 39


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