The effect of ethanol on glucose homeostasis

1978 ◽  
Vol 56 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Elizabeth A. Dittmar ◽  
G. Hetenyi Jr.
Keyword(s):  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Small Decrease ◽  
Plasma Lactate ◽  
Hepatic Glucose ◽  
Infusion Method ◽  
Elevated Rate ◽  
Diabetic Dogs ◽  
Lactate Levels

The effect of an intravenous infusion of ethanol was examined on the rates of hepatic glucose production (Ra) and overall glucose utilization (Rd) in conscious dogs in the postabsorptive state under basal conditions and in insulin-induced hypoglycaemia, after a 4-day fast or in diabetes. The rates were calculated by a tracer infusion method with 3H-labelled glucose as the tracer. The concentrations of glucose, lactate, insulin, and ethanol in plasma or blood were determined, and the rate of ethanol utilization estimated. The infusion of 0.04 or 0.24–0.29 mmol ethanol/kg per minute did not change the concentration of glucose in normal or diabetic dogs in the postabsorptive state, whereas a small decrease in fasted dogs was observed especially when ethanol was infused at the lower rate. Plasma lactate levels were increased; insulin levels did not change. Ra was transiently decreased in fasted dogs, but not in the postabsorptive state in normal or diabetic animals. Ethanol had no effect on the magnitude of the increase in Ra during insulin-induced hypoglycaemia. The estimated rate of ethanol utilization was reduced by fasting but not in diabetes. In conclusion, ethanol did not decrease the elevated rate of gluconeogenesis in diabetic dogs, nor did it interfere with the hepatic response to hypoglycaemia.

Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes

1989 ◽  
Vol 120 (3) ◽  
pp. 257-265 ◽  
Author(s):  
Ole Hother-Nielsen ◽  
Ole Schmitz ◽  
Per H. Andersen ◽  
Henning Beck-Nielsen ◽  
Oluf Pedersen
Keyword(s):  
Type Ii Diabetes ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Metformin Treatment ◽  
Obese Patients ◽  
Type Ii ◽  
Plasma Lactate ◽  
Hepatic Glucose

Abstract. Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 ± 1.2 vs 11.4 ± 1.2 mmol/l, P< 0.01) without enhancing mean day-time plasma insulin (43 ± 4 vs 50 ± 7 mU/l, NS) or C-peptide levels (1.26 ± 0.12 vs 1.38 ± 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 ± 0.16 vs 1.44 ± 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 ± 0.11 vs 1.38 ± 0.11 mmol/l, P< 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 ± 38 vs 313 ± 33 mg · m−2 · min−1, P< 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 ± 5.8 vs 50.6 ± 2.8 ml · n−2 · min−1,, P< 0.05), whereas basal hepatic glucose production was unchanged (81 ± 6 vs 77 ± 4 mg · m−2 · min−1, NS). Conclusions: 1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion. 2) The improved glycemic control during metformin treatment was associated with an enhanced insulin-mediated glucose utilization, presumably in skeletal muscle, whereas no effect could be demonstrated on hepatic glucose production.

Glucagon enhances the direct suppressive effect of insulin on hepatic glucose production in humans

1997 ◽  
Vol 272 (3) ◽  
pp. E371-E378 ◽  
Author(s):  
G. F. Lewis ◽  
M. Vranic ◽  
A. Giacca
Keyword(s):  
Type I Diabetes ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Delivery ◽  
Suppressive Effect ◽  
Type I ◽  
Constant Rate ◽  
Hepatic Glucose ◽  
Infusion Method

The present study examines the role of glucagon in modulating the hepatic and extrahepatic effects of insulin on hepatic glucose production (HGP). We infused glucagon at a constant rate (0.65 ng x kg(-1) x min(-1)) during equimolar portal and peripheral insulin delivery in seven healthy males by our previously published tolbutamide infusion method. In contrast to our previous study, in which glucagon fell by approximately 30% during hyperinsulinemia and suppression of HGP was significantly greater with equimolar peripheral than with portal insulin delivery, HGP was actually suppressed to a lesser extent with peripheral insulin delivery (69 +/- 10%) than when insulin was delivered portally (76 +/- 5%, P < 0.05). To further examine whether glucagon was enhancing the effect of portal insulin, in four additional individuals HGP was suppressed to a greater extent during a tolbutamide infusion when glucagon was administered continuously throughout the basal and hyperinsulinemic periods than when glucagon was infused during the basal period only; HGP suppressed by 63 +/- 3 vs. 52 +/- 3%, respectively, P = 0.02). Tolbutamide had no effect on HGP when infused into three C-peptide-negative individuals with type I diabetes during a low-dose insulin and glucagon infusion. These data suggest that glucagon levels are an important determinant of the balance between insulin's direct and indirect effects on HGP, with glucagon likely potentiating the direct hepatic effect of insulin.

Hypoglycemia counterregulation in elderly humans: relationship to glucose levels

1994 ◽  
Vol 267 (4) ◽  
pp. E497-E506 ◽  
Author(s):  
F. J. Ortiz-Alonso ◽  
A. Galecki ◽  
W. H. Herman ◽  
M. J. Smith ◽  
J. A. Jacquez ◽  
...  
Keyword(s):  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Severe Hypoglycemia ◽  
Glucose Production ◽  
Counterregulatory Hormones ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
Consistent Increase ◽  
Step Study ◽  
Elderly Humans

This study was designed to define the effect of human aging on hypoglycemia counterregulatory mechanisms. A hyperinsulinemic (2 mU.kg-1.min-1) glucose clamp procedure was used to control glucose and insulin levels during stepwise lowering of plasma glucose. Counterregulatory hormones, hepatic glucose production (HGP), glucose utilization, and symptoms of hypoglycemia were studied in 13 healthy young [age 24 +/- 1 (SE) yr] and 11 healthy old (age 65 +/- 1 yr) nondiabetic volunteers on two occasions: 1) at matched euglycemia and 70 and 60 mg/dl (study 1) and 2) at matched euglycemia and 60 and 50 mg/dl (study 2). The old had consistently lower epinephrine (P < 0.005), glucagon (P < 0.02), cortisol (P < 0.05), and pancreatic polypeptide (P < 0.02) responses at the 60-mg/dl glucose step in study 1. However, these differences were no longer detectable at the more severe hypoglycemic stimulus of 50 mg/dl in study 2. A consistent increase in HGP occurred in both groups only at the 50-mg/dl glucose step (study 2) and was not different between young and old. There were also no differences in symptom responses between young and old. In summary, we found that elderly individuals have a subtle impairment of the glucose counterregulatory response during moderate hypoglycemia, but this impairment is no longer detectable during more severe hypoglycemia.

The effect of insulin-induced hypogiycaemia on the secretion of glucagon and hepatic glucose production in pancreatectomized dogs

1986 ◽  
Vol 64 (11) ◽  
pp. 1440-1442 ◽  
Author(s):  
B. Lussier ◽  
G. Hetenyi Jr
Keyword(s):  
Plasma Concentration ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Alpha Cells ◽  
Pancreatic Alpha Cells ◽  
Hepatic Glucose ◽  
Ambient Concentration ◽  
Diabetic Dogs ◽  
Pancreatectomized Dogs

The concentration of plasma glucose in insulin deprived pancreatectomized dogs was decreased from the basal 385 ± 44 to 65 ± 12 mg/dL by the infusion of 7 mU∙kg−1∙min−1 insulin. During the infusion, the plasma concentration of immunoreactive glucagon (IRG) did not change and hepatic glucose production was decreased. This is in contrast to earlier findings in alloxan diabetic dogs in which plasma IRG decreased in hypoglycaemia. The hypothesis is put forward that, in contrast to pancreatic alpha cells in which the effect of insulin prevails, neither insulin nor a decrease in the ambient concentration of glucose exerts any effect on the secretion of glucagon from extrapancreatic alpha cells.

Influence of prior exercise and liver glycogen content on the sensitivity of the liver to glucagon

2002 ◽  
Vol 92 (1) ◽  
pp. 188-194 ◽  
Author(s):  
Victoria Matas Bonjorn ◽  
Martin G. Latour ◽  
Patrice Bélanger ◽  
Jean-Marc Lavoie
Keyword(s):  
Glucose Utilization ◽  
Glycogen Content ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Prior Exercise ◽  
Hepatic Glucose ◽  
Increased Sensitivity ◽  
Glucagon And Insulin

The purpose of the present study was to test the hypothesis that a prior period of exercise is associated with an increase in hepatic glucagon sensitivity. Hepatic glucose production (HGP) was measured in four groups of anesthetized rats infused with glucagon (2 μg · kg−1 · min−1 iv) over a period of 60 min. Among these groups, two were normally fed and, therefore, had a normal level of liver glycogen (NG). One of these two groups was killed at rest (NG-Re) and the other after a period of exercise (NG-Ex; 60 min of running, 15–26 m/min, 0% grade). The two other groups of rats had a high hepatic glycogen level (HG), which had been increased by a fast-refed diet, and were also killed either at rest (HG-Re) or after exercise (HG-Ex). Plasma glucagon and insulin levels were increased similarly in all four conditions. Glucagon-induced hyperglycemia was higher ( P < 0.01) in the HG-Re group than in all other groups. HGP in the HG-Re group was not, however, on the whole more elevated than in the NG-Re group. Exercised rats (NG-Ex and HG-Ex) had higher hyperglycemia, HGP, and glucose utilization than rested rats in the first 10 min of the glucagon infusion. HG-Ex group had the highest HGP throughout the 60-min experiment. It is concluded that hyperglucagonemia-induced HGP is stimulated by a prior period of exercise, suggesting an increased sensitivity of the liver to glucagon during exercise.

Phlorizin-induced normoglycemia partially restores glucoregulation in diabetic dogs

1989 ◽  
Vol 256 (2) ◽  
pp. E277-E283 ◽  
Author(s):  
G. Hetenyi ◽  
C. Gauthier ◽  
M. Byers ◽  
M. Vranic
Keyword(s):  
Hepatic Glucose Production ◽  
Plasma Catecholamines ◽  
Glucose Production ◽  
Plasma Epinephrine ◽  
Hepatic Glucose ◽  
Early Peak ◽  
Diabetic Dogs ◽  
Two Phases ◽  
Early Rise ◽  
Sympathetic Discharge

The plasma concentration of glucagon (IRG), catecholamines, and hepatic glucose production (Ra) were followed in insulin-induced hypoglycemia in dogs before (normal) and at 14-21 and again at 89-119 days after the injection of alloxan (diabetic). Some diabetic dogs were also tested when euglycemia was restored by phlorizin. In the normal state plasma IRG and epinephrine were raised by a factor of 3 and 15, respectively. Ra increased in two phases, an early peak (350% basal) was followed by a plataeu at about twice basal. In diabetes, irrespective of its duration, plasma IRG was decreased in hypoglycemia, and the rise in plasma epinephrine was significantly reduced. Ra remained unchanged. In phlorizin-treated euglycemic diabetic dogs plasma IRG fell, and the response in plasma epinephrine remained blunted. There was no early rise in Ra, but the same elevated plateau was reached at the same time as in normal animals. In conclusion, the following is observed in diabetic dogs. 1) The sensitivity of alpha-cells to insulin is maintained, but that to hypoglycemia is lost. The concentration of plasma catecholamines is raised less than in normals. With no increase in plasma glucagon this rise is not sufficient to increase Ra. 2) Restoration of euglycemia with phlorizin does not restore normal IRG and epinephrine responses to hypoglycemia but restores the delayed increase of Ra. Thus the restoration of euglycemia in severely diabetic dogs partially restores the responses of the liver, but not of the alpha-cell or sympathetic discharge, to hypoglycemia.

Effects of sustained swimming on hepatic glucose production of rainbow trout

1999 ◽  
Vol 202 (16) ◽  
pp. 2161-2166 ◽  
Author(s):  
D.S. Shanghavi ◽  
J.M. Weber
Keyword(s):  
Rainbow Trout ◽  
Glucose Utilization ◽  
Blood Glucose Concentration ◽  
Hepatic Glucose Production ◽  
Mammalian Species ◽  
Glucose Production ◽  
Glucose Kinetics ◽  
Fourfold Increase ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Hepatic Glucose

The rate of hepatic glucose production (R(a)glucose) was measured by continuous infusions of 6-[(3)H]glucose in live rainbow trout (Oncorhynchus mykiss) before, during and after swimming for 3 h at 1.5 body lengths s(−)(1) in a swim tunnel. Contrary to expectation, we found that sustained swimming causes a 33 % decline in the R(a),(glucose) of trout (from 7.6+/−2.1 to 5.1+/−1.3 (μ)mol kg(−)(1)min(−)(1), means +/− s.e.m., N=7), even though exercise of the same intensity elicits a two- to fourfold increase in all the mammalian species investigated to date. Measurements of catecholamine levels show that circulating [epinephrine] decreases by 30 % during exercise (from 4.7+/−0.3 to 3.3+/−0.4 nmol l(−)(1), N=8), suggesting that this hormone is partly responsible for controlling the decline in R(a)glucose. The inhibiting effect of swimming on hepatic glucose production persists for at least 1 h after the cessation of exercise. In addition, rainbow trout can maintain a steady blood glucose concentration throughout sustained exercise by closely matching hepatic glucose production with peripheral glucose utilization, even though this species is generally considered to be a poor glucoregulator. This study provides the first continuous measurements of glucose kinetics during the transition from rest to work in an ectotherm and it suggests that circulating glucose is not an important fuel for aerobic locomotion in trout.

Important role of glucagon during exercise in diabetic dogs

1985 ◽  
Vol 59 (4) ◽  
pp. 1272-1281 ◽  
Author(s):  
D. H. Wasserman ◽  
H. L. Lickley ◽  
M. Vranic
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Immunoreactive Insulin ◽  
Metabolic Clearance ◽  
Glucose Levels ◽  
Lower Glucose ◽  
Diabetic Dogs ◽  
Lactate Levels

To define the role of immunoreactive glucagon (IRG) during exercise in diabetes, 12 insulin-deprived alloxan-diabetic (A-D) dogs were run for 90 min (100 m/min, 12 degrees) with or without somatostatin (St 0.5 microgram . kg-1 . min-1). Compared with normal dogs, A-D dogs were characterized by similar hepatic glucose production (Ra), lower glucose metabolic clearance, and higher plasma glucose and free fatty acid levels during rest and exercise. In A-D dogs IRG was greater at rest and exhibited a threefold greater exercise increment than controls, whereas immunoreactive insulin (IRI) was reduced by 68% at rest but had similar values to controls during exercise. Basal norepinephrine, epinephrine, cortisol, and lactate levels were similar in normal and A-D dogs. However, exercise increments in norepinephrine, cortisol, and lactate were higher in A-D dogs. When St was infused during exercise in the A-D dogs, IRG was suppressed by 432 +/- 146 pg/ml below basal and far below the exercise response in A-D controls (delta = 645 +/- 153 pg/ml). IRI was reduced by 1.8 +/- 0.2 microU/ml with St. With IRG suppression the increase in Ra seen in exercising A-D controls (delta = 4.8 +/- 1.6 mg . kg-1 . min-1) was virtually abolished, and glycemia fell by 104 to 133 +/- 37 mg/dl. Owing to this decrease in glycemia, the increase in glucose disappearance was attenuated. Despite the large fall in glucose during IRG suppression, counterregulatory increases were not excessive compared with A-D controls. In fact, as glucose levels approached euglycemia, the increments in norepinephrine and cortisol were reduced to levels similar to those seen in normal exercising dogs. In conclusion, IRG suppression during exercise in A-D dogs almost completely obviated the increase in Ra, resulting in a large decrease in plasma glucose. Despite this large fall in glucose, there was no excess counterregulation, since glucose concentrations never reached the hypoglycemic range.

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