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 35 patients (13F/22M; age range 2-15 years), affected by insulin dependent diabetes mellitus (IDDM), basal and glucagon stimulated C peptide was determined and correlated with the daily insulin requirement (U/Kg/die), the glycosylated hemoglobin (HbA1c), the age of onset (months) and the length of the illness (months). The results of C peptide determinations are illustrated in tab. 1: in 20 patients (group I) the basal value of C peptide is higher than 1 ng/ml and increases after glucagon load; in 15 patients (group II) the basal value of C peptide is lower than 1 ng/ml; in 9 ones (group IIA) of these 15 a glucagon load does not elicit a residual insulin secretion; in the other 6 ones (group IIB) a significative C peptide increase is observed after glucagon load. A better metabolic control (p less than 0.01); Student t test) and a shorter length of the illness (p less than 0.05; Mann-Withney U test) was noticed in the group I in comparison with the group IIA, in which no insulin reserve, even after glucagon load, was demonstrated (tab. 2). However, no difference in the metabolic control, insulin requirement, age of onset or length of the illness resulted between group IIA and group IIB (in which an insulin reserve had been demonstrated only after glucagon load). The basal C peptide evaluation and follow up is useful in the assessment of the individual case of IDDM: a glucagon load may demonstrate a residual insulin reserve in some patients with a low basal C peptide.
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PMID:[Study of the beta cell function in type I diabetes by the determination of peptide C after glucagon challenge]. 227 34

Secondary failure to oral hypoglycemic agents (OHAs) is a possible outcome for non-insulin-dependent diabetes mellitus (NIDDM) patients and poses a serious therapeutic problem. In this study, we evaluated the effect of adding a single bedtime low-dose NPH insulin injection to the previous ineffective sulfonylurea therapy in 23 NIDDM patients with true secondary failure to OHAs. This treatment schedule was conducted for 3 mo by 18 patients (78%) who completed the study. In these patients, the addition of NPH insulin (0.2 +/- 0.01 IU/kg body wt) greatly decreased fasting and postprandial plasma glucose (P less than .001) and glycosylated hemoglobin (P less than .005). No weight gain was observed in any of the patients studied. Five patients dropped out: 2 patients (9%) due to insufficient compliance, 2 patients (9%) due to the multiple insulin injections required to achieve good metabolic control, and 1 patient (4%) due to recurrent hypoglycemic episodes. No correlation was observed between glucagon-stimulated C-peptide values and amelioration of metabolic control. In conclusion, most NIDDM patients with secondary failure to OHAs may be successfully treated with the addition of a single low-dose bedtime NPH insulin injection, and residual beta-cell function evaluation is not able to predict the effectiveness of the combined treatment.
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PMID:Low-dose bedtime NPH insulin in treatment of secondary failure to glyburide. 250 90

Dietary iron deficiency in rats results in increased blood glucose turnover and recycling. We measured the rates of glucose production in isolated hepatocytes from iron-sufficient (Fe+) and iron-deficient (Fe-) rats to assess the intrinsic capacity of the Fe- liver to carry out gluconeogenesis. Low-iron and control diets were given to 21-day-old female rats. After 4-5 wk, hemoglobin concentrations averaged 4.1 g/dl in the Fe- and 14.3 g/dl in the Fe+ animals. In the hepatocytes from Fe- rats, there was a 35% decrease in the rate of glucose production from 1 mM pyruvate + 10 mM lactate, a 48% decrease from 0.1 mM pyruvate + 1 mM lactate, a 39% decrease from 1 mM alanine, and a 48% decrease from 1 mM glycerol. The addition of 5 microM norepinephrine or 0.5 microM glucagon to the incubation media produced stimulatory effects on hepatocytes from both Fe- and Fe+ rats, resulting in the maintenance of an average difference of 38% in the rates of gluconeogenesis between the two groups. Studies on isolated liver mitochondria and cytosol revealed alpha-glycerophosphate-cytochrome c reductase and phospho(enol)pyruvate carboxykinase activities to be decreased by 27% in Fe- rats. We conclude that because severe dietary iron deficiency decreases gluconeogenesis in isolated rat hepatocytes, the increased gluconeogenesis demonstrated by Fe- rats in vivo is attributable to increased availability of gluconeogenic substrates and upregulation of the pathway.
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PMID:Iron deficiency decreases gluconeogenesis in isolated rat hepatocytes. 260 20

The aim of the present study was to analyze if an association exists between metabolic condition, C-peptide secretion and islet-cell antibody (ICA) presence in insulin-dependent diabetes mellitus (IDDM) at the clinical onset of the disease. Two hundred and nine IDDM patients were studied at diagnosis. 89% of the subjects showed residual C-peptide secretion that correlated inversely with blood glucose and glycosylated hemoglobin at diagnosis and with insulin requirement at discharge. Islet-cell antibodies were detected in 68.6% of the patients, complement-fixing ICA in 30% and insulin autoantibodies in 17.3%. Islet-cell antibody positive patients had a lower glucagon stimulated C-peptide than ICA negative subjects (0.41 +/- 0.22 versus 0.54 +/- 0.25 nmol/l, p = 0.005). However patients with high titers of ICA expressed in JDF units (JDF greater than 20) showed similar C-peptide secretion than ICA positive patients with a low level of JDF (JDF less than 20). When acid-base condition was analyzed patients on ketoacidosis at diagnosis had significant higher insulin requirement, lower C-peptide secretion and higher prevalence of ICA compared to patients that were not ketotic at diagnosis. Our findings suggest that residual beta-cell secretion plays a role on metabolic condition at diagnosis of IDDM and that ICA may be the markers of a more severe form of IDDM.
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PMID:Islet-cell antibodies: markers of a more severe insulin-dependent diabetes mellitus? 262 32

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
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PMID:The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus. 264 88

We evaluated the effectiveness of a more potent and longer-acting somatostatin analogue (SMS 201-995) as an adjunct to insulin therapy, in a double-blind placebo-controlled randomized study of 26 C-peptide-negative type I (insulin-dependent) diabetic patients (20 women, 6 men, aged 22-40 yr) on their conventional drug regimens for 12 wk. Eight patients received a low dose (10 micrograms) of the analogue, 9 received a high dose (50 micrograms) of the analogue, and 9 received placebo subcutaneously before breakfast and dinner. Twenty-four-hour serum glucose, free insulin, plasma growth hormone (GH), and glucagon profiles were obtained before and during treatment at 4-wk intervals. The mean age, duration of diabetes, daily insulin dose, and body weight were not significantly different among the groups. The mean weekly capillary blood glucose values and exogenous insulin requirements were not changed by the SMS 201-995 therapy. Mean glycosylated hemoglobin A1 levels were unchanged in both the analogue- and placebo-treated groups at wk 12. Basal and postprandial glucose, free insulin, GH, and glucagon profiles were not influenced by the SMS 201-995 therapy throughout the study. Nocturnal glucose turnover rates (D-[3-3H]glucose technique) remained unaltered by the analogue therapy. Dose-dependent gastrointestinal (GI) adverse effects (e.g., diarrhea) were documented in the analogue-treated patients. Visual acuity and fundic photomicrographs of our patients were not changed by the analogue therapy. In conclusion, the prominent adverse GI effects our patients experienced preclude the use of larger doses of the analogue that may be necessary to suppress GH and glucagon and improve glucose control in type I diabetic patients.
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PMID:Metabolic effects of long-acting somatostatin analogue (sandostatin) in type I diabetic patients on conventional therapy. 265 40

SMS 201-995 is a new somatostatin analog which is 10-60 times more potent and specific than somatostatin as an inhibitor of GH and insulin release. The aim of this study was to assess its value as an adjunct to insulin therapy in insulin-dependent diabetic- (IDD) patients. Six IDD patients were studied. Their average insulin doses ranged from 22-46 U/day, and hemoglobin A1c levels varied between 6.5-11.5%. Two patients had background retinopathy and mild sensorimotor neuropathy. After 12 h of glucemic stabilization, the patients were kept normoglycemic by connecting them to the Biostator-GCIIS. The study entailed two parts in random order, in which standardised mixed meals were administered at 0800, 1400, and 2000 h with or without sc bolus injections of 50 micrograms SMS 201-995 immediately before meal ingestion. Plasma free insulin, C-peptide, GH, and glucagon were measured by RIA. Postprandial hyperglycemia was significantly diminished by SMS 201-995 after breakfast, lunch, and dinner. Insulin requirements, both total and 2-h postprandially, decreased significantly with a parallel reduction in free insulin levels. Postprandial glucagon levels also significantly decreased, but GH profiles were similar. In conclusion, the somatostatin analog SMS 201-995 has a potential value as an adjunct to insulin in the management of IDD patients.
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PMID:Somatostatin analog SMS 201-995 and insulin needs in insulin-dependent diabetic patients studied by means of an artificial pancreas. 287 5

A randomized double-blind placebo-controlled trial was undertaken to determine whether cyclosporin enhances remission of insulin-dependent diabetes mellitus (IDDM) through the 1st yr after diagnosis. Dosage with insulin was minimized with target control of blood glucose levels less than or equal to 7.8 mM (140 mg/dl) before meals. Metabolic control was evaluated by serial determinations of glycosylated hemoglobin levels, and endogenous secretion of insulin was evaluated by determination of the levels of glucagon-stimulated insulin-connecting peptide (CP) in the plasma at 3-mo intervals. A compound definition of remission required a glucagon-stimulated CP level in plasma greater than or equal to 0.6 nM or a non-insulin-receiving state (NIR) in which target control of glycemia was maintained without administration of insulin. A clinical definition of remission required only the NIR state as defined. One hundred eighty-eight patients aged 10-35 yr entered the study within 6 wk of initiation of insulin therapy and within 14 wk of onset of symptoms and were studied for 1 yr. There were no significant differences in metabolic control between the two treatment groups during the study. The anticipated adverse effects of cyclosporin were not more frequent or severe than in other experience with the drug, but histological changes attributable to cyclosporin were present in some kidney biopsies obtained from selected patients after 1 yr. At 1 yr, by the compound definition, 33% of the cyclosporin-group and 21% of the placebo-group patients were in remission, when the corresponding rates for NIR remissions were 24 and 10%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. The Canadian-European Randomized Control Trial Group. 290 5

The effect of glucagon on hepatic regional hemodynamics was investigated in patients with chronic liver disease during peritoneoscopy with reflectance spectrophotometry. When glucagon was infused intravenously in patients with a non-cirrhotic liver, the regional hepatic tissue oxygen consumption, as estimated spectrophotometrically, increased significantly, whereas the index of hepatic tissue blood volume did not change appreciably, and consequently, the oxygen saturation of hemoglobin in the hepatic tissue blood decreased. In contrast, the administration of glucagon in patients with liver cirrhosis resulted in a significant increase in the index of hepatic tissue blood volume and produced a minor increase in hepatic tissue oxygen consumption. The oxygen saturation of hepatic blood hemoglobin tended to increase in the cirrhotics. The result suggests the presence of functional vasoconstriction at the presinusoidal and/or sinusoidal vessels in the cirrhotic liver, possibly due to a decreased vasomotor activity and/or an abnormal regulatory function of vasoactive substances, which are released by glucagon.
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PMID:Characterization of hepatic hemodynamics in cirrhotics and non-cirrhotics. Effect of glucagon infusion. 292 37

To investigate plasma glucagon counterregulatory responses to hypoglycemia, an intravenous insulin bolus was given over 2 min to 73 children, aged 8.5-18.8 yr, with diabetes duration 1.2-17.1 yr. The plasma glucagon responses of the 61 children without glucagon antibodies or abnormal glucagon molecules were compared with those of 13 nondiabetic control subjects, aged 8.3-18.3 yr. Glucagon increments from baseline (73 +/- 10 pg/ml) and peak glucagon responses (212 +/- 13 pg/ml) were markedly lower in diabetic patients than in control subjects (341 +/- 49 and 462 +/- 51 pg/ml, respectively, P less than .001). Glucagon responses were found to correlate positively with the age of the patients at the time of testing (r = .478, P less than .001) and inversely with metabolic control as measured by glycosylated hemoglobin (r = -.342, P less than .02). There was no relationship between glucagon responses and diabetes duration. There was also no relationship between the glucagon increments and free-insulin levels during the test. Glucose recovery from the nadir was impaired in diabetic subjects compared with control subjects and correlated inversely with free-insulin levels. However, glucose recovery did not correlate with the rise of plasma glucagon. Glucose recovery was not different in patients with glucagon antibodies. In this study, we have demonstrated a deficient glucagon response to hypoglycemia in children with insulin-dependent diabetes mellitus. However, the clinical significance of this deficit is not clear.
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PMID:Glucagon responses to hypoglycemia in children and adolescents with IDDM. 306 2


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