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)

We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201-995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 +/- 6.5 yr, daily insulin requirement 36 +/- 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 micrograms of SMS 201-995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201-995 and placebo. Postmeal glycemic peaks were decreased after SMS 201-995 (119.6 +/- 5.4 mg/dl vs 149.1 +/- 4.2; p less than 0.05) as well as insulin requirements (3.2 +/- 0.8 U vs 13.3 +/- 1.9; p less than 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 +/- 6 pg/ml vs 59 +/- 24; p less than 0.05) and so GH level only 180 min after lunch (p less than 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201-995 may be mainly mediated by the suppression of postprandial glucagon peak.
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PMID:Effects of a somatostatin derivative (SMS 201-995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device. 267 Nov 12

The prevention or correction of hypoglycemia is the result of both dissipation of insulin and activation of counterregulatory systems. In the models studied to date, glucagon and epinephrine have been shown to be the key counterregulatory factors; the potential roles of other hormones, neural factors, or substrate mechanisms in other models and during more gradual recovery from hypoglycemia remain to be defined. Deficient glucagon responses to decrements in plasma glucose, which are common in patients with IDDM and occur in some patients with NIDDM, result in altered counterregulation. But counterregulation is generally adequate, because epinephrine compensates for it. Defective glucose counterregulation due to combined deficiencies of glucagon and epinephrine secretory responses occurs in many patients, typically those with longstanding diabetes, and must be added to the list of factors known to increase the risk of hypoglycemia, at least during intensive therapy. From the material reviewed, it should be apparent that much has been learned about glucose counterregulation. It should be equally clear that much remains to be learned. Among the many possibilities, we consider four worthy of emphasis. First of all, we need to examine the physiology and pathophysiology of glucose counterregulation in additional models (e.g., during exercise) and over longer periods. Secondly, we need to determine whether central nervous system adaptation to antecedent glycemia occurs and, if so, identify its mechanisms. Thirdly, we need to develop better methods of insulin delivery or learn to correct or compensate for defective counterregulatory systems, if we are to achieve euglycemia safely in diabetic patients with defective glucose counterregulation. Finally, we need to know whether effective control of diabetes mellitus prevents development of defective glucose counterregulation.
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PMID:Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. 286 65

The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex- and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 +/- 2.5 to 31.1 +/- 3.9 pmol/l (P less than 0.01) and 19.7 +/- 1.7 to 23.9 +/- 3.4 pmol/l respectively after 10 min (P less than 0.01). The plasma glucagon concentrations increased from 27 +/- 4.7 to 176 +/- 23.1 pmol/l (P less than 0.01) and 36 +/- 5.0 to 302 +/- 31.9 pmol/l (P less than 0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.
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PMID:Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function. Increased plasma SRIF in IDDM. 286 13

The effect of a new octapeptide analogue of somatostatin (SMS 201-995) on blood glucose and gut hormone levels was studied in 10 C-peptide-negative, insulin-dependent diabetic (IDDM) subjects. On separate days, either 50 or 100 micrograms SMS or placebo was s.c. injected simultaneously with an identical insulin dose 30 min before a mixed meal. Postprandial blood glucose decreased after 100 micrograms SMS s.c. within 30 min from 8.9 +/- 0.7 to 7.8 +/- 0.6 mmol/L (P less than 0.001) and remained at similar levels during 180 min. In contrast, postprandial blood glucose concentration increased after placebo from 9.9 +/- 0.8 to 13.8 +/- 0.9 mmol/L (SMS versus placebo P less than 0.001). Plasma glucagon decreased rapidly after SMS to the limit of detection (P less than 0.001) and remained lowered during 180 min; in contrast, glucagon levels increased after the meal during the placebo study (SMS versus placebo P less than 0.001). Plasma growth hormone concentrations were significantly lower after SMS than after placebo (P less than 0.05). SMS abolished completely the postprandial increase in plasma gastrin and pancreatic polypeptide (PP) concentrations. Plasma free fatty acid (FFA) and triglyceride concentrations decreased after SMS, reaching significantly lower levels than after placebo (P less than 0.05 and P less than 0.01), respectively). Plasma SMS concentration increased rapidly after s.c. administration of SMS; its appearance preceded that of plasma free insulin after s.c. insulin injection. Fifty micrograms SMS was similarly effective as 100 micrograms in decreasing blood glucose, triglycerides, glucagon, and gut hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced postprandial hyperglycemia after subcutaneous injection of a somatostatin-analogue (SMS 201-995) in insulin-dependent diabetes mellitus. 286 93

To further study the elevated plasma somatostatin (SRIF)--and reduced plasma glucagon concentrations found in IDDM patients without residual B-cell function compared to normal controls, we investigated 39 such patients, randomly assigned to three different insulin treatment regimens; conventional therapy with two injections a day (CTh), insulin pump (CSII) and multiple injections (MI), for 1 year. They were given an arginine infusion (0.5 g/kg/20 min). The mean basal plasma SRIF values in the CTh, CSII and MI groups were 20.8 +/- 3.3, 18.6 +/- 1.8 and 20.6 +/- 2.8 pmol/l and the mean basal plasma glucagon values were 30 +/- 5.7, 19 +/- 2.3 and 27 +/- 4.7 pmol/l, respectively. Both SRIF and glucagon increased in all groups in relation to arginine infusion. For both hormones, the mean values were highest in the CTh group, lowest in the CSII group, although the differences were not significant. The mean HbA1 values for the last 3 months within the test were 10.0 +/- 0.5, 8.8 +/- 0.3 and 9.1 +/- 0.5%, respectively, in the same order as above. The CTh group had significantly higher HbA1 values than the CSII group (p less than 0.02). We conclude that small differences in long-term blood glucose control are of inconsiderable importance for the islet hormonal response to arginine found in IDDM without B-cell function.
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PMID:Plasma somatostatin and plasma glucagon in long-term IDDM without residual B-cell function. No effect of different long-term metabolic control. 287 90

The use of hospital services was studied in 228 patients with known diabetes (KD) (52 insulin treated. 101 diet plus oral hypoglycaemic agents (OHAs), 66 diet treated and 9 without treatment) and 87 subjects with fasting hyperglycaemia (FH) found by screening of a well-defined population aged 60-74 years. Ninety per cent were NIDDM as evaluated by a high C-peptide response on glucagon stimulation. Information about all admissions during the year before ascertainment was obtained from the complete regional computerized hospital registration system. The overall average admission rate per year for KD males was 0.47 and for females 0.50. The average number of bed-days occupied per person-year was 6.8 for KD males and 8.2 for females. These rates are 2-3 times higher than those of the general population. Insulin treated NIDDM patients had a rate of 23.9, whereas IDDM patients had a rate of 15.2 bed-days per person-year. The corresponding figures for patients treated with OHAs were 3.5 and for patients treated with diet 4.6. FH had overall bed-day occupancy rates of 0.50 and 1.09 for males and females, respectively, which was less than half of that expected from the general population. IF discharge diagnosis (principal and/or subsidiary) had been used for identification of hospitalized patients with diabetes the bed-days used by KD patients would have been underestimated by 15.3%, most pronounced for diabetics treated with OHAs (21.1%) or diet (21.6%).
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PMID:Use of hospital services by elderly diabetics: the Frederica study of diabetic and fasting hyperglycaemic patients aged 60-74 years. 295 43

Hormonal and glycemic changes in 22 rhesus monkeys were characterized during the first days after treatment with streptozotocin (STZ) (45 to 55 mg/kg, administered intravenously [IV]). Almost half (10/22) of the monkeys developed insulin-dependent diabetes mellitus (STZ-IDDM) within five days following injection. Four of the remaining monkeys did not become insulin dependent for at least 6 months after STZ treatment, during which time they were considered non-insulin-dependent, and eight monkeys never required exogenous insulin. In the STZ-IDDM group, plasma immunoreactive c-peptide (IRC-P) levels fell by three hours after STZ from a mean +/- SEM of 252 +/- 82 to 101 +/- 45 pg/mL, as glucose and immunoreactive glucagon (IRG) levels increased from 65 +/- 3 and 120 +/- 37, respectively, to 336 +/- 43 mg/dL and 234 +/- 52 pg/mL, respectively. Between six and 30 hours after treatment, IRC-P increased to a peak of 1,561 +/- 360 pg/mL before falling permanently to less than 60 pg/mL by 66 hours. During this period, glucose and IRG responded in a reciprocal fashion by falling and then increasing to levels above 300 mg/dL and 300 pg/mL, respectively, by 66 hours. In the non-insulin-dependent diabetes mellitus (STZ-NIDDM) group, no clear reciprocal relationship between IRC-P and glucose and IRG was obtained. In nine additional monkeys subjected to total pancreatectomy (Px), IRC-P and IRG levels fell immediately and permanently by greater than 90% and 75%, respectively. Levels of immunoreactive somatostatin increased steadily over the initial 96 hours following STZ, but did so both STZ-IDDM and Px monkey groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective beta cell destruction. 296 84

An insulin-producing cell line, Clone-16, of hamster origin, was characterized for islet hormone production and for reactivity with islet cell surface (ICSA) and islet cell cytoplasmic (ICA) antibodies in sera from children with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM). The Clone-16 cells have a doubling time of about 50-60 hr. The cells produced 63 +/- 3 ng (mean +/- SD) immunoreactive insulin and 9.4 +/- 0.3 ng immunoreactive glucagon per day per 10(6) cells, while somatostatin (SRIF) and pancreatic polypeptide (PP) were undetectable. The reactivity with autoantibodies in IDDM sera was assessed by indirect immunofluorescence or 125I-protein A binding assay on intact cells to detect islet cell surface antibodies (ICSA) or on frozen sections of cell pellets to detect islet cell cytoplasmic antibodies (ICCA) by indirect immunofluorescence. Although the proportion of the ICSA-positive Clone-16 cells compared favorably with rat islet cells (r = 0.81; p less than 0.01), we found 5/10 IDDM sera to be positive on rat islet cells but 8/10 on the Clone-16 cells. There was also a good correlation in the 125I-protein A binding assay between mouse islet cells and Clone-16 cells (r = 0.91; p less than 0.01). Frozen sections of Clone-16 cells showed a cytoplasmic immunofluorescence in 8/10 of the IDDM sera and this reaction parallelled the results obtained in the standard indirect immunofluorescence assay with a frozen section of human blood group O pancreas. We conclude that the insulin- and glucagon-producing Clone-16 cells are a useful cell line for detecting islet cell autoantibodies.
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PMID:Detection of islet cell autoantibodies in newly diagnosed diabetic patients using insulin-producing Syrian hamster cells. 330 Nov 57

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.
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PMID:Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis. 330 47

The purpose of the present study was to evaluate the insulin requirement in response to sucrose meal in IDDM and its modulation by a disaccharidase inhibitor, Acarbose. After an overnight fast, the subjects (n = 9) were "hooked" to the artificial pancreas (Biostator) to maintain normoglycemia. Blood glucose and insulin requirement were recorded by the Biostator throughout the experiment. The patients were divided into two groups. In group I, five patients received increasing sucrose load (50, 75 and 100 g) with and without Acarbose 100 mg. After a 50 g sucrose meal with and without Acarbose, the peak postprandial (PP) blood glucose was 118 and 157 mg/dl and the insulin requirement was 3.9 and 7.8 units resulting in free plasma insulin peak of 34 and 59 microU/ml respectively. After a 75 g sucrose meal with and without Acarbose, the peak PC blood glucose was 134 and 166 mg/dl and the insulin requirement was 5.7 and 9.9 units resulting in free plasma insulin peak of 75 and 87 microU/ml. After a 100 g sucrose meal with and without Acarbose the peak PP blood glucose was 131 and 175 mg/dl and the insulin requirement was 6 and 12.8 units resulting in free plasma insulin peak of 50 and 69 microU/ml. In group II, four patients received increasing Acarbose dose with a fixed sucrose load (75 g). The PP blood glucose peaked at 161, 145, 120 and 102 mg/dl after 0, 50, 100, 200 mg of Acarbose respectively. The total insulin requirements were 12.9, 9.6, 4.3 and 3.1 units. The free plasma insulin was decreased by Acarbose treatment while plasma glucagon remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of sucrose meal on insulin requirement in IDDM and its modulation by acarbose. 352 70


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