A physiological increase in the hepatic glycogen level does not affect the response of net hepatic glucose uptake to insulin.
To determine the effect of an acute increase in hepatic glycogen on net hepatic glucose uptake (NHGU) and disposition in response to insulin in vivo, studies were performed on two groups of dogs fasted 18 h. During the first 4 h of the study, somatostatin was infused peripherally, while insulin and glucagon were replaced intraportally in basal amounts. Hyperglycemia was brought about by glucose infusion, and either saline (n = 7) or fructose (n = 7; to stimulate NHGU and glycogen deposition) was infused intraportally. A 2-h control period then followed, during which the portal fructose and saline infusions were stopped, allowing NHGU and glycogen deposition in the fructose-infused animals to return to rates similar to those of the animals that received the saline infusion. This was followed by a 2-h experimental period, during which hyperglycemia was continued but insulin infusion was increased fourfold in both groups. During the initial 4-h glycogen loading period, NHGU averaged 1.18 +/- 0.27 and 5.55 +/- 0.53 mg x kg(-1) x min(-1) and glycogen synthesis averaged 0.72 +/- 0.24 and 3.98 +/- 0.57 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively (P < 0.05). During the 2-h hyperinsulinemic period, NHGU rose from 1.5 +/- 0.4 and 0.9 +/- 0.2 to 3.1 +/- 0.6 and 2.5 +/- 0.5 mg x kg(-1) x min(-1) in the saline and fructose groups, respectively, a change of 1.6 mg x kg(-1) x min(-1) in both groups despite a significantly greater liver glycogen level in the fructose-infused group. Likewise, the metabolic fate of the extracted glucose (glycogen, lactate, or carbon dioxide) was not different between groups. These data indicate that an acute physiological increase in the hepatic glycogen content does not alter liver glucose uptake and storage under hyperglycemic/hyperinsulinemic conditions in the dog.
Winnick
Jason J
JJ
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6015, USA. jason.winnick@vanderbilt.edu
An
Zhibo
Z
Moore
Mary Courtney
MC
Ramnanan
Christopher J
CJ
Farmer
Ben
B
Shiota
Masakazu
M
Cherrington
Alan D
AD
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D004285:Dogs; D005632:Fructose / Q000494:pharmacology; D005934:Glucagon / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism* / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D005632:Fructose; D019344:Lactic Acid; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose