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)

This is the first report to describe prolonged continuous subcutaneous insulin infusion in a massively obese insulin-resistant pregnant woman with type II diabetes. Maternal 24-hour plasma glucose levels became normal by 48 hours, and normoglycemia was maintained with high daily doses of insulin (530 U-333 U/24 hours) from 29 weeks' gestation until delivery at 38.5 weeks. Excellent diabetic control was associated with euglycemia, normal glycosylated hemoglobin concentration, and a significant decrease in mean 24-hour plasma C-peptide (P less than .004) and glucagon (P less than .003) levels. Unexpectedly, fetal growth accelerated during constant insulin infusion despite normal maternal plasma glucose levels. The newborn infant was large (4530 g), with a striking truncal accumulation of fat, hypoglycemia (30-minute plasma glucose 11 mg/dL), and polycythemia (central venous hematocrit 71%). Normalization of maternal plasma glucose levels failed to ameliorate established macrosomia, and did not prevent the neonatal complications that are common in infants of diabetic mothers.
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PMID:Continuous subcutaneous insulin infusion in an obese insulin-resistant pregnant woman with type II diabetes: accelerated fetal growth and neonatal complications. 362 9

A thiol peptidase that catalyzes at near neutral pH the hydrolysis of insulin, the isolated A and B chains of insulin, and glucagon was purified from rat liver cytosol by fractionation on Sephadex G-200, Affi-Gel Blue, and Spherogel TSK-G 3000 SW. The purified enzyme showed a single component by chromatography on a Spherogel TSK column and by gel filtration on a Sephadex G-200 column. The native enzyme has a molecular weight of approximately 180,000 and consists of two subunits having pI's of 5.9 and 6.3. Studies on its substrate specificity showed that the purified enzyme degrades glucagon, insulin, insulin B chain, and insulin A chain, but it does not degrade proinsulin, ACTH, or denatured hemoglobin. Kinetic analyses were performed on three substrates. The Km values were: 34 nM for insulin, 276 nM for insulin B chain, and 3.5 microM for glucagon. The kcat and Vm/Km values were glucagon greater than B chain greater than insulin. Thus, the enzyme has the highest affinity/lowest efficiency for insulin, an intermediate affinity/intermediate efficiency for B chain of insulin and the lowest affinity/highest efficiency for glucagon. The effect of several potential activators and inhibitors on the enzyme's activity was investigated. The enzyme activity was markedly inhibited by N-ethylmaleimide, p-chloromercuribenzoic acid, iodoacetamide, and Np-tosyl-L-phenylalanine chloromethyl ketone (TPCK), and was partially inhibited by dithiothreitol, by the chelating agents EDTA and EGTA, and by phenylmethylsulfonyl fluoride (PMSF). Bacitracin inhibited the activity of the enzyme, but the protease inhibitors aprotinin, leupeptin, pepstatin, and phosphoramidon had little or no effect. Reduced glutathione, iodoacetate, and N alpha,p-tosyl-L-lysine chloromethyl ketone (TLCK) also had little or no effect on the enzyme activity.
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PMID:Purification and characterization of a rat liver cytosol neutral thiol peptidase that degrades glucagon, insulin, and isolated insulin A and B chains. 388 Oct 83

Continuous subcutaneous insulin infusion (CSII) has been compared with conventional insulin injection treatment (CIT) supplemented by self-monitoring of capillary blood glucose (SMBG) in 18 nonobese adults with insulin-dependent diabetes mellitus (IDDM). Mean daily insulin dosage and rates of hypoglycemia were similar during CSII (duration of treatment 36 +/- 2 wk mean +/- SE) and CIT (31 +/- 1.6 wk). On the basis of fasting C-peptide concentrations and postintravenous glucagon increments of less than 0.1 pmol/ml, subjects were classified C-peptide negative (CP NEG) (N = 11), or C-peptide positive (CP POS) (N = 7). Relative to CIT, CP NEG subjects on CSII had significant decreases in premeal/bedtime and postmeal plasma glucose concentrations and glycosylated hemoglobin (percent of total). CP POS patients during each of CSII and CIT showed glycemic responses equivalent to those of CP NEG patients on CSII. In neither group could results be explained on the basis of improved beta cell function. Thus, therapeutic advantage of CSII was not apparent in IDDM adults retaining significant C-peptide activity.
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PMID:Continuous subcutaneous insulin infusion in adults: glycemic advantage is predicted by venous plasma C-peptide concentrations. 390 23

Azathioprine (2 mg/kg) was given, in addition to routine insulin treatment, to alternate patients presenting with recent-onset type I diabetes. Treated (N = 13) and untreated (N = 11) patients did not differ significantly at diagnosis with respect to age, duration of symptoms, body weight, blood glucose, hemoglobin A1c, or presence of ketosis. Eight patients were treated for 12 mo, three elected to stop treatment at 6 mo, and treatment was stopped in two because of side effects. Seven treated patients had a remission compared with one untreated patient. At 12 mo these seven patients were distinguished by significantly higher basal and glucagon-stimulated levels of C-peptide (1.98 +/- 0.52 and 3.88 +/- 0.34 micrograms/L, respectively) compared with the other six treated patients (0.93 +/- 0.52 and 1.32 +/- 0.85 microgram/L, respectively), and by the persistence of islet cell cytoplasmic antibodies. Remissions were not sustained in the 1-2 yr after treatment, although relapsed patients required less insulin for control. These results corroborate those from nonrandomized trials using cyclosporine and suggest that protracted treatment with nonspecific immunosuppressive drugs may be necessary to avert insulin dependence.
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PMID:Increase in remission rate in newly diagnosed type I diabetic subjects treated with azathioprine. 390 63

The effect of feeding high amounts of polyols on rat metabolism was studied. Adult male rats were fed the basal diet or the same diet to which had been added either galactitol, mannitol or xylitol for 8 wk (final polyol level 200 g/kg diet). Although all three polyols retarded the growth rate of the animals, the polyols were well tolerated. The four experimental groups did not differ significantly (P greater than 0.01) in the following analyses: blood lactic acid and serum transaminases, amylase, lactate dehydrogenase, triglycerides, insulin, glucagon and corticosterone. Compared to rats fed the basal diet, galactitol rats had higher blood hemoglobin levels (P less than 0.01); those fed galactitol or mannitol had lower blood glucose (P less than 0.001 and P less than 0.01, respectively), and those fed mannitol had higher blood pyruvic acid (P less than 0.01). Rats fed any of the polyols had lower serum total cholesterol and liver ascorbic acid (P less than 0.001) than control rats. Rats fed mannitol had higher liver glycogen levels (P less than 0.001) than control rats. Irrespective of the structural differences between the pentitol and the hexitols, a number of common metabolic effects were found. The proposed mechanisms of these effects include 1) the slow absorption and the rapid intraluminal metabolism of the polyols and 2) the similar handling of these polyols in the liver by a dehydrogenase.
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PMID:Metabolic effects in rats of high oral doses of galactitol, mannitol and xylitol. 392 94

The risk of severe hypoglycemia associated with the particular therapeutic approach of two University hospitals was assessed in 96% of all patients with insulin-dependent diabetes mellitus (IDDM) who had been admitted during a period of almost 3 yr to the diabetic wards of two hospitals and who participated in a structured teaching and treatment program. During a mean follow-up period of 18 mo, 10% of the conventionally treated patients (N = 384; age 30 +/- 13 yr; duration of diabetes 12 +/- 9 yr) and 9% of the CSII-treated patients (N = 50, age 28 +/- 7 yr, duration of diabetes 13 +/- 7 yr, total follow-up period 1093 patient-mo) experienced at least one severe hypoglycemic episode per year, and a total of 123 severe hypoglycemic episodes occurred. In a subgroup of 169 conventionally treated patients, mean glycosylated hemoglobin values decreased from 10.5 +/- 1.9% before participation in the program to 9.2 +/- 2.0% (P less than 0.001) 18 +/- 4 mo thereafter. For the CSII-treated patients, glycosylated hemoglobin values were 9.7 +/- 1.9% before initiation of pump therapy and remained at the upper normal range from 3 mo thereafter throughout the study. There was no relationship between glycosylated hemoglobin levels and the occurrence of severe hypoglycemic episodes. Fifty-three severe hypoglycemic episodes were treated with glucagon injections by the patients' relatives (all but one effectively), 30 were managed by assisting physicians, and 44 led to hospitalization. Thus, successful attempts to improve glycosylated hemoglobin values in an unselected group of patients with IDDM were not associated with an unduly high risk of severe hypoglycemia when compared with the scarce data from the literature.
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PMID:Incidence and management of severe hypoglycemia in 434 adults with insulin-dependent diabetes mellitus. 400 60

The effects of norepinephrine and glucagon on gluconeogenesis were studied in hemoglobin-free perfused liver from rats kept for 1-20 days at 4 degrees C. When rats were starved for 24 h at 4 degrees C, the plasma glucose level of rats exposed to cold for 5, 10, and 20 days was significantly higher than that of rats for 1 day, but hepatic glycogen decreased to the same level in all groups. In the isolated perfused liver, basal rates of oxygen consumption and glucose production increased slightly through 5 days of cold exposure and returned to control levels after 20 days of cold exposure. The rates of glucose production from lactate, pyruvate, sorbitol, and glycerol increased by 20-30% after 5 days of cold exposure. The stimulation of gluconeogenesis from these substrates by norepinephrine and phenylephrine increased markedly at all time periods from 1 to 20 days in the cold, with a maximum at 5 days. The stimulation of glycogenolysis by norepinephrine was not affected by cold exposure. The response to catecholamines decreased markedly in liver perfused with calcium-free medium and/or with phentolamine. The stimulation of gluconeogenesis by glucagon increased only in rats exposed to cold for 20 days. The results obtained suggest that the stimulation of hepatic gluconeogenesis by cold is due to an alpha-adrenergic response, and the activation occurs beyond the interaction of norepinephrine with its receptor.
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PMID:Effect of norepinephrine on gluconeogenesis in perfused livers of cold-exposed rats. 403 79

Glucose counter-regulatory capacity and the hormonal responses to insulin-induced hypoglycemia were studied in eight type 1 diabetics before and after improvement of metabolic control by continuous subcutaneous insulin infusion (CSII). The intensified treatment resulted in a decrease in mean glycosylated hemoglobin from 11.6 +/- 0.5 to 9.3 +/- 0.4% within a mean period of 14 weeks. During a constant rate infusion of insulin (2.4 U/h), steady state levels of glucose appeared in all subjects. The steady state glucose level was identical before and after CSII. The counter-regulatory hormonal responses showed significantly higher epinephrine levels, while glucagon, growth hormone, and cortisol were not influenced. In parallel with the heightened epinephrine response the pulse rate response was significantly enhanced. The restitution of blood glucose after insulin hypoglycemia was not modified. It is concluded that a more vigorous catecholaminergic response to hypoglycemia is achieved after improved metabolic control by CSII.
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PMID:Effect of improved glycemic control by continuous subcutaneous insulin infusion on hormonal responses to insulin-induced hypoglycemia in type 1 diabetics. 405 May 45

The energy requirement for protein breakdown in Escherichia coli results from an ATP requirement for the function of protease La, the product of the lon gene. This novel serine protease contains an ATPase activity that is essential for proteolysis. ATP and protein hydrolysis show the same Km for ATP (30-40 muM) and are affected similarly by various inhibitors, activators, and ATP analogs. Vanadate inhibited ATP cleavage and caused a proportionate reduction in casein hydrolysis, and inhibitors of serine proteases reduced ATP cleavage. Thus, ATP and protein hydrolysis appear to be linked stoichiometrically. Furthermore, ATP hydrolysis is stimulated two- to threefold by polypeptides that are substrates for the protease (casein, glucagon) but not by nonhydrolyzed polypeptides (insulin, RNase). Unlike hemoglobin or native albumin, globin and denatured albumin stimulated ATP hydrolysis and were substrates for proteolysis. It is suggested that the stimulation of ATP hydrolysis by potential substrates triggers activation of the proteolytic function.
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PMID:Protease La from Escherichia coli hydrolyzes ATP and proteins in a linked fashion. 621 87

The aims of the present study were to compare various methods for assessment of residual insulin production and to evaluate its role in the metabolic regulation in insulin-dependent, type I diabetes mellitus. Glycosylated hemoglobin (HbA1) was used as a measure of the long-term glycemic control. Twenty-eight patients with type I diabetes mellitus with onset before the age of 30 and with a duration of less than 6 years were studied. C-peptide in plasma in the fasting state, after glucagon stimulation, and the 24-hour urinary excretion were measured. Fasting plasma C-peptide was detected in 61%, and 39% showed a significant rise after glucagon stimulation. The increment correlated negatively with HbA1 (rs = -0.57, p less than 0.001), as did the 24-hour urinary excretion (rs = -0.61, p less than 0.001). The 16 patients with urinary C-peptide values of at least 1 nmol had a mean HbA1 of 8.9 +/- 0.3%, as opposed to 11.6 +/- 0.5% for those excreting less (p less than 0.001). Measurement of the 24-hour urinary excretion of C-peptide provides a reliable method for evaluating residual insulin secretion.
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PMID:Residual C-peptide production in type I diabetes mellitus. A comparison of different methods of assessment and influence on glucose control. 636 38


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