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.

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.

scholarly journals Functional Improvement in -Islet Cells and Hepatocytes with Decreasing Deuterium from Low Carbohydrate Intake in a Type-II Diabetic

2021 ◽  
Vol 9 (6) ◽  
Author(s):  
Edwin Jones ◽  
Cortney Jardet
Keyword(s):  
Type Ii Diabetes ◽  
Islet Cells ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Functional Improvement ◽  
Type Ii ◽  
Hepatic Glucose ◽  
Low Carbohydrate ◽  
History Of ◽  
Glucose Tolerance Tests

A 59-year-old patient with a 18-year history of type-II diabetes is presented who showed dramatic improvements to glucose tolerance tests and increased fasting hepatic glucose production with systemic deuterium depletion. Deuterium, which is well known to decrease the efficiency of the ATP syntheses nanomotors, is likely the mechanism leading to the systemic changes to both insulin and hepatic glucose production in the pancreas and liver, respectively. Systemic deuterium depletion occurs with consumption of low carbohydrate (keto) diets and deuterium depleted water.

scholarly journals Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver

2020 ◽  
Vol 117 (12) ◽  
pp. 6733-6740 ◽  
Author(s):  
Thiago M. Batista ◽  
Sezin Dagdeviren ◽  
Shannon H. Carroll ◽  
Weikang Cai ◽  
Veronika Y. Melnik ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Glycogen Accumulation ◽  
Hepatic Glucose ◽  
Glucose Output

Insulin action in the liver is critical for glucose homeostasis through regulation of glycogen synthesis and glucose output. Arrestin domain-containing 3 (Arrdc3) is a member of the α-arrestin family previously linked to human obesity. Here, we show thatArrdc3is differentially regulated by insulin in vivo in mice undergoing euglycemic-hyperinsulinemic clamps, being highly up-regulated in liver and down-regulated in muscle and fat. Mice with liver-specific knockout (KO) of the insulin receptor (IR) have a 50% reduction inArrdc3messenger RNA, while, conversely, mice with liver-specific KO ofArrdc3(L-Arrdc3KO) have increased IR protein in plasma membrane. This leads to increased hepatic insulin sensitivity with increased phosphorylation of FOXO1, reduced expression of PEPCK, and increased glucokinase expression resulting in reduced hepatic glucose production and increased hepatic glycogen accumulation. These effects are due to interaction of ARRDC3 with IR resulting in phosphorylation of ARRDC3 on a conserved tyrosine (Y382) in the carboxyl-terminal domain. Thus,Arrdc3is an insulin target gene, and ARRDC3 protein directly interacts with IR to serve as a feedback regulator of insulin action in control of liver metabolism.

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.

scholarly journals Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

Diabetes ◽  
2013 ◽  
Vol 62 (7) ◽  
pp. 2266-2277 ◽  
Author(s):  
K. Kimura ◽  
Y. Nakamura ◽  
Y. Inaba ◽  
M. Matsumoto ◽  
Y. Kido ◽  
...  
Keyword(s):  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

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.

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.

The synthetic human growth hormone fragment (32–38) increases glucose uptake in the conscious dog

1988 ◽  
Vol 117 (4) ◽  
pp. 457-462 ◽  
Author(s):  
Ralph W. Stevenson ◽  
Nowell Stebbing ◽  
Theodore Jones ◽  
Keith Carr ◽  
Peter M. Jones ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Control Period ◽  
Human Growth ◽  
Glucose Production ◽  
Independent Action ◽  
Conscious Dog ◽  
Hepatic Glucose

Abstract. hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol · kg−1 · min−1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0–180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined ([3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 ± 0.17 to 5.78 ± 0.17 mmol/l with hGH32-38; 5.50 ± 0.22 to 5.50 ± 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135– 180 min) (74.9 ± 12.7 vs 43.7 ± 7.1 μmol · kg−1 · min−1, P < 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.

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