scholarly journals Vitamin D Deficiency Induces Insulin Resistance and Re‐Supplementation Attenuates Hepatic Glucose Output via the PI3K‐AKT‐FOXO1 Mediated Pathway

2020 ◽  
Vol 64 (1) ◽  
pp. 1900728 ◽  
Author(s):  
Shivaprakash Jagalur Mutt ◽  
Ghulam Shere Raza ◽  
Markus J Mäkinen ◽  
Sirkka Keinänen‐Kiukaanniemi ◽  
Marjo‐Riitta Järvelin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output

Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance

2002 ◽  
Vol 282 (2) ◽  
pp. E386-E394 ◽  
Author(s):  
Hiroki Sugita ◽  
Masao Kaneki ◽  
Eriko Tokunaga ◽  
Michiko Sugita ◽  
Chieko Koike ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Glycogen Phosphorylase ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The molecular mechanisms underlying endotoxin-induced insulin resistance remain unclear. Endotoxin or lipopolysaccharide (LPS) injection is a potent stimulator of inducible nitric oxide synthase (iNOS). This study in rats, using the specific iNOS inhibitor aminoguanidine, investigated the role of iNOS in endotoxin-induced hyperglycemia and insulin resistance. LPS injection led to hyperglycemia, insulin resistance, and increased iNOS protein expression and activity. Aminoguanidine prevented LPS-induced hyperglycemia without affecting insulin levels or iNOS expression. Aminoguanidine attenuated the LPS-induced insulin resistance, reflected by the requirement for a higher glucose infusion rate to maintain euglycemia during a hyperinsulinemic clamp study. Aminoguanidine completely blocked the LPS-elevated hepatic glucose output and also inhibited LPS-induced increases in hepatic glycogen phosphorylase activities and phospho enolpyruvate carboxykinase (PEPCK) mRNA expression, key enzymes for glycogenolysis and gluconeogenesis, respectively. Thus, these data demonstrate an important role for iNOS in LPS-induced insulin resistance, evidenced by the attenuation of LPS-induced hyperglycemia and reversal of increased hepatic glucose output by aminoguanidine. The protective effect of aminoguanidine on insulin resistance is probably by attenuation of hepatic glucose output via its inhibition of key enzymes for glycogenolysis and gluconeogenesis, including glycogen phosphorylase and PEPCK.

Increased net hepatic glucose output from gluconeogenic precursors after high-sucrose diet feeding in male rats

1997 ◽  
Vol 272 (2) ◽  
pp. R526-R531 ◽  
Author(s):  
M. J. Pagliassotti ◽  
P. A. Prach
Keyword(s):  
Insulin Resistance ◽  
Glucose Production ◽  
Male Rats ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Sucrose Diet ◽  
High Sucrose Diet ◽  
Glucose Output ◽  
High Sucrose

A high-sucrose diet reduces the ability of insulin to suppress hepatic glucose production (hepatic insulin resistance) in rats. The purpose of the present study was to investigate the contribution of hepatic gluconeogenesis to sucrose-induced hepatic insulin resistance. Single-pass liver perfusions were performed on 24-h food-deprived male Wistar rats after 8 wk on either a high-corn starch (ST; 68% of energy) or high-sucrose (SU; 68% of energy) diet. Hepatic glucose output (HGO, micromol of glucose x min(-1) x g(-1)) in the presence of lactate, alanine, or dihydroxyacetone (DHA) was used as an estimate of gluconeogenic capacity, because liver glycogen levels after the 24-h fast were negligible (<1.2 mg/g). HGO was significantly (P < 0.05) greater in SU vs. ST at all concentrations of lactate, alanine, and DHA. Maximal rates of HGO were 1.9 +/- 0.4 and 2.8 +/- 0.3 at 10 mM lactate, 0.6 +/- 0.2 and 1.4 +/- 0.3 at 10 mM alanine, and 1.7 +/- 0.3 and 2.6 +/- 0.2 at 20 mM DHA in ST and SU, respectively. When HGO was matched between SU and ST with the use of different precursor concentrations, there was a significant (P < 0.05) reduction in the ability of insulin (175 microU/ml) to suppress HGO in SU vs. ST. These data suggest that sucrose feeding increases gluconeogenesis from lactate, alanine, and DHA and that this route of glucose production is resistant to insulin suppression.

Metabolic Effects of Metformin in Humans

2019 ◽  
Vol 15 (4) ◽  
pp. 328-339 ◽  
Author(s):  
María M. Adeva-Andany ◽  
Eva Rañal-Muíño ◽  
Carlos Fernández-Fernández ◽  
Cristina Pazos-García ◽  
Matilde Vila-Altesor
Keyword(s):  
Insulin Resistance ◽  
Glycogen Synthesis ◽  
Metabolic Effects ◽  
Hepatic Glycogen ◽  
Insulin Deficiency ◽  
Indirect Pathway ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Patients With Diabetes ◽  
Glucose Output

Background: Both insulin deficiency and insulin resistance due to glucagon secretion cause fasting and postprandial hyperglycemia in patients with diabetes. Introduction: Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive. Results: Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen synthesis from “de novo” synthesized glucose) owing to insulin deficiency and glucagoninduced insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production. In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity. Accordingly, metformin preserves β-cell function in patients with type 2 diabetes. Conclusion: Several mechanisms have been proposed to explain the metabolic effects of metformin, but evidence is not conclusive and the molecular basis of metformin action remains unknown.

Beta-adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor

1993 ◽  
Vol 264 (5) ◽  
pp. R984-R991 ◽  
Author(s):  
C. H. Lang
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Tumor Necrosis ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Necrosis Factor

The macrophage secretory product tumor necrosis factor (TNF) impairs insulin action on peripheral glucose uptake and hepatic glucose output. Because circulating catecholamines are also elevated by TNF, the present study was performed to determine the role of the adrenergic system in eliciting the insulin resistance. Human recombinant TNF (1 microgram.h-1.kg-1) was infused intravenously into chronically catheterized fasted rats for approximately 18 h. Before TNF, an infusion of either saline, propranolol (nonselective beta-antagonist), atenolol (selective beta 1-antagonist), or phentolamine (alpha-antagonist) was started and continued throughout the experimental protocol. Infusion of either the alpha- or beta-receptor antagonist failed to prevent the TNF-induced increase in basal glucose uptake or hepatic glucose output. Under euglycemic hyperinsulinemic conditions, whole body glucose disposal was lower in TNF-infused rats than in control animals. This resulted from a decreased rate of insulin-stimulated glucose uptake by skeletal muscle, skin, and intestine. In propranolol-infused rats, but not in those receiving atenolol or phentolamine, the TNF-induced decrease in whole body glucose uptake was partially prevented. Propranolol attenuated the development of peripheral insulin resistance by selectively preventing the decrease in glucose uptake by skeletal muscle but not by skin and ileum. Propranolol was also able to ameliorate the hepatic insulin resistance produced by TNF. These results suggest that beta-adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.

Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men

Diabetes ◽  
1991 ◽  
Vol 40 (8) ◽  
pp. 1033-1040 ◽  
Author(s):  
J. N. Clore ◽  
P. S. Glickman ◽  
S. T. Helm ◽  
J. E. Nestler ◽  
W. G. Blackard
Keyword(s):  
Control Mechanism ◽  
Dual Control ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics

Diabetes ◽  
1987 ◽  
Vol 36 (3) ◽  
pp. 274-283 ◽  
Author(s):  
A. D. Baron ◽  
L. Schaeffer ◽  
P. Shragg ◽  
O. G. Kolterman
Keyword(s):  
Type Ii ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Type Ii Diabetics ◽  
Glucose Output

Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin

Diabetes ◽  
1995 ◽  
Vol 44 (9) ◽  
pp. 1038-1045 ◽  
Author(s):  
K. Rebrin ◽  
G. M. Steil ◽  
L. Getty ◽  
R. N. Bergman
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output
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