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)

Since the isolation of enkephalins 7 yr ago, there has been an explosive increase in knowledge and an enormous interest in the action of both exogenous and endogenous opiates. This review deals with the interaction of opiates with the endocrine pancreas. The results of animal studies performed in vitro do not allow any conclusion to be drawn, because the effects of opioid peptides on pancreatic hormone release seem dependent on many variables, including the agent investigated, dose administered, concentration of glucose in the medium, and experimental procedure used. The results of in vivo animal studies suggest that central administration of opiates and opioid peptides acts indirectly via the sympathetic nervous system to cause hyperglycemia and impaired insulin secretion, while peripheral administration tends to stimulate insulin and glucagon secretion. This last statement seems also to be true for studies performed in human beings. The narcotic addict offers a model to evaluate the hormonal and metabolic effects of a chronically administered agent that binds and activates endogenous receptors. In these subjects, it is possible to find increased concentrations of glycosylated hemoglobin A1 and a marked reduction of the acute insulin response to intravenous glucose, but not to arginine, which suggests a state of defective glucose recognition by pancreatic beta-cells during narcotic addiction. Thus, the heroin addict, like patients with non-insulin-dependent diabetes, does not respond appropriately to glucose signals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphine, opioid peptides, and pancreatic islet function. 636 56

The counterregulatory response to insulin-induced hypoglycemia was investigated in 22 insulin-dependent diabetics (IDD) with recurrent hypoglycemia and in 6 healthy volunteers. Hypoglycemia was induced by a constant rate infusion of insulin (2.4 U/h) up to four hours. Conventional insulin therapy was changed to an i.v. infusion of regular insulin 24 hours prior to the experiment. The presence of diabetic autonomic neuropathy was evaluated by respiratory sinus arrhythmia and Valsalva maneuver. In healthy subjects, blood glucose was decreased to 2.5 mmol, here reaching steady state level and giving rise to marked glucagon and growth hormone (GH) responses. The majority of IDD (group A) reached a slightly lower steady state glucose level and exhibited similar glucagon and GH responses while the epinephrine response was augmented. Six IDD (group B) showed a continuous decrease in blood glucose to 1.2 +/- 0.1 mmol/l at which level the infusion of insulin was discontinued due to neuroglucopenic symptoms. These subjects had no glucagon and epinephrine responses while their GH and cortisol responses were normal. A comparison of the diabetic groups revealed a longer duration of diabetes and a more impaired autonomic nervous function in group B while glycosylated hemoglobin was similar. It is concluded that most IDD have normal hormonal responses (epinephrine, glucagon, GH, cortisol) and normal counterregulartory capacity to hypoglycemia induced by a prolonged infusion of a moderate dose of insulin. Some patients with long-term diabetes and impaired capacity to counteract hypoglycemia exhibit deficient glucagon and epinephrine responses to hypoglycemia.
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PMID:Impaired counter regulation of hypoglycemia in a group of insulin-dependent diabetics with recurrent episodes of severe hypoglycemia. 638 51

Twenty-four diabetic patients receiving insulin were randomized to 3 groups. Group I began self blood glucose monitoring by meter and switched to visually read strips at 3 months. Group II began self blood glucose monitoring by visually read strips and switched to meter readings at 3 months. Group III monitored urine glucoses for the 6 months of the trial. Professional interaction time was the same for all patients and each patient was placed on the same insulin delivery scheme (3 shots NPH and/or regular). Mean C-peptide levels 6 min following intravenous glucagon was comparable in all 3 groups. Patients monitoring blood glucose showed a significant decrease in glycosylated hemoglobin values (p less than 0.01) from patients monitoring urine at 6 months of the trial. Patients subjectively felt meters were more accurate than visual strips but both groups I and II showed lower glycosylated hemoglobin levels (p less than 0.02 at 6 months) and sequence analysis revealed no sequence effect. The trial confirms that blood glucose monitoring technologies have advantages over urine monitoring in helping patients achieve improved glucose levels. Patients perform equally well in terms of blood glucose "control" whether visually read strips or meters are used for initial teaching or maintenance if patients are instructed appropriately in each methodology. These findings have economic implications for large scale treatment programs.
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PMID:A randomized comparative crossover evaluation of glucose monitoring technologies. 652 91

There has been concern regarding the susceptibility of patients on continuous subcutaneous insulin infusion (CSII) to hypoglycemic episodes. This study has examined glycemic control, the frequency of hypoglycemic reactions and the counterregulatory response to an IV insulin infusion fo 2.4 units per hour in five brittle insulin-dependent diabetics before and during CSII. CSII was associated a significant reduction in glycosylated hemoglobin, standard deviation of blood glucose estimations and daily insulin dosage. The frequency of symptomatic hypoglycemic reactions was reduced (mean 14/4 weeks pre CSII, 5/4 weeks post CSII, p less than 0.05). However, after CSII the IV insulin caused a more rapid fall in blood glucose from the physiological to the hypoglycemic range while growth hormone and cortisol responses were both reduced (p less than 0.05) and the deficient glucagon response was not improved. Thus, although the frequency of reported hypoglycemic reactions was reduced by CSII, susceptibility to hypoglycemia due to excess insulin delivery was enhanced, owing to increased insulin sensitivity and/or additional impairment of the counterregulatory response.
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PMID:Hypoglycemic episodes during continuous subcutaneous insulin infusion: decreased frequency but increased susceptibility. 659 16

Twenty insulin-dependent diabetic patients participated in a 1-yr prospective randomized cross-over study comparing multiple subcutaneous injections (MSI) and continuous subcutaneous insulin infusion (CSII) complemented by home blood glucose monitoring. While 4 patients dropped out early, 16 patients completed the study. Patients had severe insulin deficiency documented by absent C-peptide response to glucagon stimulation. A marked improvement in control was observed when mean blood glucose and glycosylated hemoglobin A1 were compared with conventional therapy. No significant differences in the degree of metabolic control achieved, as measured by mean fasting, preprandial, and postprandial capillary blood glucose (CBG), M values, glycosylated hemoglobin A1 concentration, cholesterol and triglyceride levels were seen between MSI and CSII in the sixteen patients who completed the study. However, individual comparisons showed that fasting CBG and M-values were lower under CSII than MSI in seven patients (P less than 0.05). In contrast, two patients exhibited lower M values under MSI than under CSII (P less than 0.01), while for the remaining seven patients the results were similar. After completion of the study, two patients went back to conventional insulin therapy, seven patients remained on the pump, and seven patients chose to stay on MSI. In conclusion, on a long-term basis, the two methods can produce comparable levels of blood glucose and glycosylated hemoglobin in ambulatory insulin-dependent diabetics.
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PMID:Comparison between continuous subcutaneous insulin infusion and multiple injections of insulin. A one-year prospective study. 675 42

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.
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PMID:Hormonal and metabolic effects of a pancreatic endocrine graft. Vascularized segmental transplantation in insulin-dependent diabetic patients. 679 5

Nonhuman primates have been used for a variety of studies on diabetes mellitus. Spontaneous, natural forms of diabetes have been well documented in several species; there are limited data on numerous other species that indicate diabetes or a diabetes-like syndrome. The causes and manifestations of spontaneous diabetes, their prevalence, and their severity vary among species. Diabetes has also been induced in nonhuman primates with streptozotocin, alloxan, hypothalamic lesions, or pancreatectomy. The extent and severity of metabolic and hormonal abnormalities vary according to the method of induction, the individual monkey, and the species. Metabolic, hormonal, and pathologic abnormalities present in human diabetics also occur in monkeys with either spontaneous or induced diabetes. Hyperglycemia and impaired glucose clearance are common, lipid concentrations are elevated, and hemoglobin A1c concentrations are increased in hyperglycemic monkeys. Monkeys may have fasting hypo- or hyperinsulinemia; insulin responses are often impaired in glucose tolerance tests. Glucagon concentrations may be increased. Aortic atherosclerosis, muscle capillary microangiopathies, cataracts, and glomerulosclerosis have been documented. Primate size and longevity allow longitudinal studies with procedures that may not be feasible in smaller animals or in human beings. Nonhuman primates may be the models of choice for studies on selected aspects of diabetes and its secondary complications.
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PMID:Nonhuman primates as models for the study of human diabetes mellitus. 681 70

In 20 patients who underwent open-heart surgery, the plasma concentrations of glucose, insulin, glucagon, growth hormone, free hemoglobin, and cholinesterase were measured before, during and after pulsatile and continuous perfusion. Pulsatile flow was achieved by modification of a roller pump to effect rapid acceleration and slowing. The driving motor was interfaced with a control module to enable ECG-triggered perfusion. In addition to the clinical studies, investigations were performed in 9 dogs to assess the effects of pulsatile and continuous perfusion on liver and pancreas flow during total bypass. During pulsatile perfusion there was a significant increase in insulin which, however, was clearly diminished in relation to glucose levels. The response of the beta-cells was markedly more compromised after continuous than pulsatile perfusion. The secondary postoperative increase in insulin can be accounted for by intravenous administration of glucose and, particularly, after pulsatile perfusion, indicates an almost completely normal response of pancreatic beta-cells. As opposed to the effects of continuous perfusion, the low glucose, glucagon, and growth hormone levels, the insulin increase during and after pulsatile perfusion as well as normal cholinesterase values observed in association with pulsatile perfusion appear to be the result of improved pancreatic and hepatic function. This contention is supported by the experimental finding of significantly increased pancreas and liver perfusion during pulsatile perfusion.
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PMID:[Clinical and experimental studies on pulsatile and continuous flow during extracorporeal circulation (author's transl)]. 700 92

Previous studies have shown that a neutral metallo-endopeptidase purified from rat kidney degrades the B chain of insulin, glucagon, ACTH and, at a markedly slower rate, the A chain of insulin. In contrast the enzyme does not attack native insulin, oxytocin, vasopressin, ribonuclease, albumin or denatured hemoglobin. The current studies demonstrate that the neutral peptidase also degrades the isolated C-peptide of proinsulin and cleaves certain peptide bonds in and near the C-peptide moiety of native proinsulin. Time courses of the formation of fluorescamine-reactive material during digestion of proinsulin and isolated C-peptide with the peptidase were identical. However, structural analysis of the peptidase-digested proinsulin showed that the enzyme does not convert proinsulin to insulin but that the peptidase cleaves one bond, Tyr26-Thr27, in the B chain moiety and five bonds in the C-peptide moiety, producing four split proinsulins. One of the split proinsulins is des-octacosa-peptide (27-54) porcine proinsulin or des-tetracosapeptide (27-50) bovine proinsulin. Each is a derivative of the insulin molecule having an extension of nine residues (ten residues in the case of the derivative from bovine proinsulin) at the N-terminus of A chain and lacking four residues at the C-terminus of B chain. This two chain derivative retains full immunoreactivity with insulin antibodies and exhibits 2.4-times more biological activity (promotion of glycogenesis in primary cultured hepatocytes) than proinsulin and about two-thirds the activity of insulin.
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PMID:Degradation of proinsulin and isolated C-peptide by rat kidney neutral metallo-endopeptidase. 702 23

To assess the possible value of the use of high-purity pork insulin (HPPI) in the United States, the serum insulin (I), pancreatic polypeptide (PP), glucagon (G), and somatostatin (SRIF) antibody binding characteristics have been determined in 90 conventional insulin-treated diabetic subjects and related to their degree of metabolic control, as assessed by glycosylated hemoglobin (HbA1) concentration. All diabetic subjects had antibodies to insulin, but there was no relationship between any of the antibody binding characteristics and HbA1 level: 47% possessed PP antibodies; mean +/- SEM HbA1 in these patients was 14.5 +/- 0.3%, identical to those without PP antibodies (14.5 +/- 0.4%); 10% had G binding antibodies with HbA1 levels of 14.6 +/- 0.8%, similar to those without G antibodies. No subject possessed SRIF antibodies. This lack of correlation between antibody characteristics and metabolic control makes it unlikely that, in the majority of patients, treatment with a less immunogenic insulin (HPPI) versus conventional insulin will result in improved diabetic control.
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PMID:Insulin, pancreatic polypeptide, and glucagon antibodies in insulin-dependent diabetes mellitus. 704 10


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