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 influence of a hypertonic saline infusion on the counterregulatory response to insulin-induced hypoglycemia in nine normal men. When given hypertonic saline, the men had less hypoglycemia in response to insulin, both acutely and in the recovery phase (P less than 0.01), and released 34% more glucagon (P less than 0.05) than when they were water loaded. The total integrated ACTH, cortisol, epinephrine, norepinephrine, and GH responses to hypoglycemia were similar after saline and water loading. After the saline load, the mean plasma vasopressin level rose from 11.0 +/- 2.2 (+/- SEM) to 20.9 +/- 2.9 pg/mL in response to insulin-induced hypoglycemia. In contrast, after the water load, vasopressin levels were undetectable (less than 2 pg/mL) and they increased only to 2.6 +/- 0.4 pg/mL with hypoglycemia. There was a significant positive correlation between basal plasma vasopressin and nadir glucose concentrations and a significant negative correlation between basal plasma vasopressin and the integrated fall in glucose after insulin administration (P less than 0.01 and P less than 0.025, respectively). The difference in the glycemic response to insulin may be related to the high vasopressin levels after saline loading, which could, either directly and/or through enhanced glucagon release, increase hepatic glucose production and thus limit the hypoglycemic response to insulin.
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PMID:Influence of infused hypertonic saline on the response to insulin-induced hypoglycemia in man. 303 50

Eighteen lean adult volunteers with insulin-requiring diabetes mellitus attempted to achieve normoglycemia using continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) in a randomized crossover trial of 68 +/- 2.5 weeks (mean +/- SEM) duration. As reported (Diabetes Care 8: 447-55, 1985) the group with absent to low beta-cell function (C-peptide negative, n = 11) attained mean post-absorptive normoglycemia only during CSII vs CIT (p less than 0.05). Only following CSII was this without change in post-absorptive serum triglyceride concentrations (-4 +/- 5.6 vs 12 +/- 4.7 mg/dl; -0.04 +/- 0.6 vs 0.14 +/- 0.05 mM, p less than 0.05) or body weight (0.01 +/- 0.02 vs 0.05 +/- 0.01 kg/week, p less than 0.05). In the group with glucagon stimulated serum C-peptide 100-400 pmol/L (C-peptide positive) responses to CSII or CIT were equal. As total daily insulin dosage (0.05 +/- 0.04 U/kg/day) was the same under all conditions, to explain the efficacy of CSII, glucoregulatory hormone responses were examined. Pre- and post-test breakfast serum free immunoreactive insulin and plasma glucagon concentrations were essentially unaffected by C-peptide or treatment status. Erythrocyte 125I-insulin binding was decreased in the C-peptide negative group only during CSII (8.6 +/- 0.5 vs 10.1 +/- 0.7%, p less than 0.005); C-peptide positive group receptor binding was consistently low (8.2 +/- 0.8, 8.4 +/- 0.9%). During CIT using intermediate-acting insulin post-lunch peripheral venous insulin failed to rise (p less than 0.05), but in the C-peptide positive group, on the basis of C-peptide responses to breakfast an undetected rise and fall of portal venous insulin was assumed to coincide with each meal. Thus, only during CIT in the C-peptide negative group, which received on average 6.4/wk/subject fewer pre-meal regular insulin boluses (p less than 0.01), was the frequency of meal-related change in portal insulinemia decreased. Consistent meal-related fluctuations in portal insulinemia inherent in CSII hepatocytes sensitized by a post-receptor mechanism to the suppressive effects of insulin on glucose output and thus were indirectly responsible for the observed improvement in glycemic control and lipid metabolism in the C-peptide negative group.
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PMID:Metabolic effects of continuous subcutaneous insulin infusion: evidence that a rise and fall of portal vein insulin concentration with each major meal facilitates post-absorptive glycemic control. 304 15

Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone-treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone-treated rats the fasting alpha-amino-N concentrations were lower: 4.0 +/- 0.3 mmol/l (mean +/- SEM) versus 6.8 +/- 0.3 mmol/l in controls. The capacity of Urea-N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7 +/- 1.7 mumol/(min 100 g), after 14 days of treatment 7.9 +/- 0.8 mumol/(min 100 g), and in controls 7.5 +/- 1.0 mumol/(min 100 g) (mean +/- SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino-N conversion, implying that more amino-N than normal is eliminated as urea-N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.
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PMID:Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats. 304 15

Rats weighing 220 g were injected sc with zinc protamin glucagon 20 micrograms once daily (recurrent hyperglucagonemia) and zinc protamin glucagon 60 micrograms three times daily (chronic hyperglucagonemia); the controls received the vehicle three times daily. In the first group blood glucagon rose to above 200 ng/liter for 5 h every day; in the second group it constantly stayed above 600 ng/liter. After both 2 (n = 5) and 14 (n = 5) days treatment the control total blood alpha-amino-nitrogen (AAN) concentration was 4.3 +/- 0.1 mmol/liter, and the urea nitrogen synthesis rate was 4.9 +/- 0.4 mumol/(min.100 g BW) (mean +/- SEM) in controls. In recurrent hyperglucagonemic rats, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 3.6 +/- 0.2 mmol/liter (P less than 0.05 vs. control) and urea nitrogen synthesis rate 4.5 +/- 0.8 mumol/(min.100 g BW). In chronic hyperglucagonemic, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 2.2 +/- 0.1 mmol/liter (P less than 0.05 vs. control) and UNSR 7.9 +/- 0.8 mumol/(min.100g BW) (P less than 0.05 vs. control). The urea excretion was identical in controls and during recurrent hyperglucagonemia, but it was increased by 50% during chronic hyperglucagonemia. Food intake was the same in all groups. N Balances decreased from 10 mmol/24 h to 5 mmol/24 h (P less than 0.05) by chronic hyperglucagonemia. The total organ N content did not change by recurrent hyperglucagonemia, but in chronic hyperglucagonemia it decreased to 65-85% (P less than 0.01) in carcass, intestines, liver, and kidneys. In conclusion chronic but not recurrent hyperglucagonemia increases the rate of urea synthesis and decreases the blood amino acid concentration. This is suggested to be a reason for the loss of N from organs by chronic hyperglucagonemia.
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PMID:Loss of nitrogen from organs in rats induced by exogenous glucagon. 304 48

Euglycaemic clamp experiments with single or combined infusions of human biosynthetic proinsulin and insulin were performed in 6 healthy, normal weight subjects in order to assess the possibility of antagonistic, additive, or synergistic effects on whole body glucose metabolism. Insulin (i: 2.02 pmol x kg-1 x min-1) or proinsulin (p: 9.26 pmol x kg-1 x min-1) were infused under euglycaemic clamp conditions over 240 min. After 120 min, the infusion rates were doubled (protocols ii and pp), or proinsulin (protocol ip) or insulin (protocol pi) infusions were added. After 240 min of infusing insulin or proinsulin alone, euglycaemia was maintained for an additional 60 min period without hormone infusions to measure the decay of hormone concentrations and of effects on glucose metabolism. Effects on glucose uptake were measured as the glucose infusion rate necessary to maintain euglycaemia. IR-insulin, IR-proinsulin, IR-C-peptide and IR-glucagon were determined by specific radioimmunoassays. After 240 min, similar steady state glucose infusion rates were reached for all protocols (mean +/- SEM, mg x kg-1 x min-1: ii: 10.6 +/- 1.0; ip: 9.1 +/- 0.4; pi: 10.0 +/- 0.9; pp: 8.4 +/- 0.7). The infusion rate with proinsulin alone (pp), however, was significantly smaller than with insulin alone (ii), indicating a somewhat lower effectiveness of the proinsulin dose employed. With all protocols, nonesterified fatty acid and IR-glucagon concentrations were decreased to a similar extent. Steady state hormone concentrations were reached within 30 min of each infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of single and combined infusions of human biosynthetic proinsulin and insulin on glucose metabolism and on plasma hormone concentrations in euglycaemic clamp experiments. 305 14

Oral glucose tolerance tests were conducted in 10 noninsulin-dependent diabetic and 14 healthy control subjects with a 75-g glucose load. The tests were repeated 1 week later with 43 g of ethanol mixed with the glucose. Blood samples were analyzed for ethanol, glucose, insulin, C-peptide, and glucagon levels. The blood ethanol peak was nearly equal in diabetic and control subjects (mean +/- SEM values of 55 +/- 8 and 48 +/- 6 mg/dl 45 min after ethanol ingestion). Ethanol did not affect glucose tolerance in either of the study groups. Mean +/- SEM values of the sum of the increment above the baseline glucose level were 659 +/- 48 vs. 675 +/- 76 mg/dl with or without ethanol in diabetics and 227 +/- 35 vs. 244 +/- 36 mg/dl in control subjects. The plasma insulin and C-peptide responses to glucose were delayed in diabetic patients compared to controls but were not affected by ethanol. In vitro, ethanol, at a concentration of 100 mg/dl or greater, significantly decreased insulin binding to erythrocytes in a dose-related manner. Scatchard analysis of competitive insulin binding to erythrocytes indicated that ethanol reduced insulin binding affinity (1.6 +/- 0.5 vs. 4.2 +/- 0.8 x 10(8)/M), but not binding capacity (4.5 +/- 2.4 vs. 4.4 +/- 1.7 nM, with and without ethanol, respectively).
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PMID:Effect of alcohol on glucose tolerance in normal and noninsulin-dependent diabetic subjects. 306 31

We studied the methyl acceptor capacity of insulin and glucagon in vitro. The levels of carboxylmethylation of pancreatic hormones (dpm x 10(3], when incubated with S-adenosyl-L-(3H-methyl)-methionine as methyl donor and purified protein carboxylmethylase, were: insulin (n = 6) 8.1 +/- 0.2 and 11.1 +/- 1.5 (mean +/- SEM) for 0.25 and 1.0 mg/ml, respectively; glucagon (n = 6) 17.0 +/- 3.2 and 40.2 +/- 2.5 (mean +/- SEM) for 0.5 and 1.0 mg/ml, respectively. On a molar basis, the methyl acceptor capacity was 1.0 dpm/pmol for insulin and 9.5 dpm/pmol for glucagon. Polyacrylamide gel electrophoresis of carboxylmethylated hormones showed a radioactivity (3H-methyl) peak that co-migrated with the corresponding 125I-hormone. Glucagon, but not insulin, seems to be a relatively good substrate for carboxylmethylation.
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PMID:Carboxylmethylation of insulin and glucagon in vitro. 306 84

In order to study the effect of hyperglucagonaemia on nitrogen metabolism in diabetes, zinc protamine glucagon 60 micrograms was injected subcutaneously 3 times daily for 4 weeks into streptozotocin diabetic rats (n = 5), adequately treated with long acting insulin. This raised the plasma concentration of glucagon to 725 +/- 125 (mean +/- SEM), which is not different from that found in portal blood of uncontrolled diabetic rats: 400 +/- 75 ng/l. The controls were 5 diabetic rats treated with insulin alone and 5 non-diabetic rats. Compared with control rats the nitrogen balance was reduced (p less than 0.05) and the nitrogen contents of carcass, heart, intestines, and kidneys were reduced by 15-30% (p less than 0.05) in the glucagon treated rats. The hepatic capacity of urea synthesis and the alanine elimination rate were determined in the 3 above-mentioned groups, and confirmed in 3 identical groups followed for only 2 weeks; and in addition in a group of glucagon treated diabetic rats, where the long acting glucagon was substituted by neutral insulin the last two days before investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exogenous hyperglucagonaemia in insulin controlled diabetic rats increases urea excretion and nitrogen loss from organs. 306 29

Arterial and hepatic venous blood levels of glucose were studied in 12 dogs during orthotopic liver transplantation performed under ketamine anesthesia without exogenous glucose administration. During the early part of surgery, arterial blood glucose levels were stable: 161 +/- 12 mg/dl (mean +/- SEM) after laparotomy and 183 +/- 16 mg/dl 5 min before the anhepatic stage. During the anhepatic stage, arterial blood glucose levels decreased progressively to 135 +/- 9 and 88 +/- 8 mg/dl, 5 min in the anhepatic stage and 5 min before reperfusion of the graft liver, respectively (P less than 0.05). Reperfusion of the graft liver resulted in an increase in arterial glucose levels to 206 +/- 17 and 240 +/- 24 mg/dl, 5 and 30 min after reperfusion, respectively (P less than 0.05). Hepatic venous blood glucose levels increased after reperfusion (405 +/- 37 and 346 +/- 41 mg/dl, 5 and 30 min after reperfusion, respectively) and were significantly higher than in arterial blood (P less than 0.05). Arterial plasma insulin, measured in five animals, did not change significantly during the procedure, whereas plasma glucagon levels, stable during the preanhepatic and anhepatic stages, increased steadily after reperfusion of the graft liver, from 66.1 +/- 14.2 to 108.4 +/- 38.1 pg/ml (P less than 0.05). This study shows that in dogs with ketamine anesthesia mild hypoglycemia occurs during the anhepatic stage of liver transplantation without exogenous glucose administration followed by hyperglycemia on reperfusion of the graft liver, possibly secondary to the release of glucose from the donor liver.
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PMID:Glucose metabolism during liver transplantation in dogs. 309 1

The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in malnourished adult patients receiving parenteral nutrition with constant nitrogen intake and high or low glucose intakes for 8 day periods. Energy balance, nitrogen balance, weight and temperature were determined daily. Blood samples taken at admission and at the end of days 7 and 8 of each diet were analysed for glucose, fatty acids, urea, insulin, glucagon and thyroid hormones. The effect of increasing glucose intake was to increase nitrogen balance by 0.28 +/- 0.08 (SEM) mg/kJ. A scheme is proposed, based on present and previous findings, of the separate effects of nitrogen and energy intake on nitrogen balance, permitting calculation of rates of repletion of fat and lean body mass from estimates of nitrogen intake and energy balance. Malnourished patients are shown to attain markedly positive nitrogen balances at zero or negative energy balances. Large errors in estimation of energy requirements have little effect on nitrogen balance. Changes in nitrogen balance were entirely due to changes in urea excretion. Creatinine excretion increased 12% with high glucose intake, attributed mainly to increased muscle mass (7%) and body temperature (4%). A 12% increase in resting energy expenditure was only partly due to costs of glycogen storage and lipogenesis; the remainder, about one-half, is probably due to glucose and insulin mediated increases in sympathetic activity. There were marked increases in 3,5,3'-triiodothyronine (T3) concentrations with time, but no difference between the high and low glucose diets. The T3/thyroxine ratio, an index of free T3 concentration, increased much more rapidly on the high than on the low glucose diet. Changes in T3 could not account for the effect of glucose, under these conditions, to increase resting energy expenditure.
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PMID:Effects of increasing glucose intake on nitrogen balance and energy expenditure in malnourished adult patients receiving parenteral nutrition. 310 72


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