Balancing Hepatic Glucose Disposal and Production

2004 ◽  
pp. 379-397 ◽  
Author(s):  
R. Yang ◽  
C.B. Newgard
Keyword(s):  
Glucose Disposal ◽  
Hepatic Glucose

Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase

1993 ◽  
Vol 264 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
L. Rossetti ◽  
S. Farrace ◽  
S. B. Choi ◽  
A. Giaccari ◽  
L. Sloan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glycogen Synthase ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Intracellular Glucose

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min-1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP-glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism.

scholarly journals Coordinated Regulation of Hepatic Glucose Disposal

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
David Anthony Okar ◽  
W Ed Smith ◽  
Sara Langer ◽  
Simone Baltrusch
Keyword(s):  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Coordinated Regulation

Intraportal administration of neuropeptide Y and hepatic glucose metabolism

2008 ◽  
Vol 294 (4) ◽  
pp. R1197-R1204 ◽  
Author(s):  
Makoto Nishizawa ◽  
Masakazu Shiota ◽  
Mary Courtney Moore ◽  
Stephanie M. Gustavson ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Neuropeptide Y ◽  
Glucose Uptake ◽  
Infusion Rate ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Intravenous Glucose ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

We examined whether intraportal delivery of neuropeptide Y (NPY) affects glucose metabolism in 42-h-fasted conscious dogs using arteriovenous difference methodology. The experimental period was divided into three subperiods (P1, P2, and P3). During all subperiods, the dogs received infusions of somatostatin, intraportal insulin (threefold basal), intraportal glucagon (basal), and peripheral intravenous glucose to increase the hepatic glucose load twofold basal. Following P1, in the NPY group ( n = 7), NPY was infused intraportally at 0.2 and 5.1 pmol·kg−1·min−1 during P2 and P3, respectively. The control group ( n = 7) received intraportal saline infusion without NPY. There were no significant changes in hepatic blood flow in NPY vs. control. The lower infusion rate of NPY (P2) did not enhance net hepatic glucose uptake. During P3, the increment in net hepatic glucose uptake (compared with P1) was 4 ± 1 and 10 ± 2 μmol·kg−1·min−1 in control and NPY, respectively ( P < 0.05). The increment in net hepatic fractional glucose extraction during P3 was 0.015 ± 0.005 and 0.039 ± 0.008 in control and NPY, respectively ( P < 0.05). Net hepatic carbon retention was enhanced in NPY vs. control (22 ± 2 vs. 14 ± 2 μmol·kg−1·min−1, P < 0.05). There were no significant differences between groups in the total glucose infusion rate. Thus, intraportal NPY stimulates net hepatic glucose uptake without significantly altering whole body glucose disposal in dogs.

Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs

2003 ◽  
Vol 284 (5) ◽  
pp. E1027-E1036 ◽  
Author(s):  
Makoto Nishizawa ◽  
Mary Courtney Moore ◽  
Masakazu Shiota ◽  
Stephanie M. Gustavson ◽  
Wanda L. Snead ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Glucose Disposal ◽  
Control Group ◽  
Hepatic Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference ◽  
Intraportal Infusion

Arteriovenous difference and tracer ([3-3H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7–36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol · kg−1 · min−1in eight dogs, at 10 and 20 pmol · kg−1 · min−1in seven dogs, and at 0 pmol · kg−1 · min−1in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol · kg−1 · min−1[21.8 vs. 13.4 μmol · kg−1 · min−1(control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol · kg−1 · min−1[87.3 ± 8.3 and 105.3 ± 12.8, respectively, vs. 62.2 ± 5.3 and 74.7 ± 7.4 μmol · kg−1 · min−1(control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased ( P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol · kg−1 · min−1(22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol · kg−1 · min−1(25 and 46% greater than control) and tended ( P = 0.1) to increase during GLP-1 infusion at 20 pmol · kg−1 · min−1(24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.

Effects of acute running exercise on whole body insulin action in obese male SHHF/Mcc-facp rats

1994 ◽  
Vol 77 (2) ◽  
pp. 534-541 ◽  
Author(s):  
J. Gao ◽  
W. M. Sherman ◽  
S. A. McCune ◽  
K. Osei
Keyword(s):  
Heart Failure ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Insulin Responsiveness ◽  
Obese Male

This study utilized the obese male spontaneously hypertensive heart failure rat (SHHF/Mcc-facp), which has metabolic features very similar to human non-insulin-dependent diabetes mellitus. The purpose of this study was to assess the insulin sensitivity and responsiveness of whole body glucose disposal and insulin suppressability of hepatic glucose production with use of the euglycemic-hyperinsulinemic clamp procedure in 12- to 15-wk-old SHHF/Mcc-facp rats at rest (OS) and 2.5 h after a single session of acute exercise (OE). Lean male SHHF/Mcc-facp rats were sedentary (LS) control animals. At least three clamps producing different insulin-stimulated responses were performed on each animal in a randomized order. At this age the obese animals are normotensive and have not developed congestive heart failure. Compared with LS, OS were significantly hyperglycemic and hyperinsulinemic and insulin sensitivity and responsiveness of whole body glucose uptake and insulin suppressability of hepatic glucose production were significantly decreased. Compared with LS and OS, acute exercise significantly decreased resting plasma glucose but did not alter plasma insulin. Compared with OS, acute exercise significantly increased the insulin responsiveness of whole body glucose disposal but did not affect the sensitivity of whole body glucose disposal or insulin suppressability of hepatic glucose production. Compared with LS, however, acute exercise did not “normalize” the insulin responsiveness of whole body glucose disposal. Thus a single acute exercise session improves but does not normalize whole body insulin resistance in the SHHF/Mcc-facp rat.

Modeling glucose disposal in diabetic dogs fed mixed meals

1984 ◽  
Vol 246 (1) ◽  
pp. E52-E61
Author(s):  
Y. Yamasaki ◽  
J. Tiran ◽  
A. M. Albisser
Keyword(s):  
Experimental Data ◽  
Mathematical Model ◽  
Insulin Infusion ◽  
Glucose Disposal ◽  
Mean Square ◽  
Mixed Meal ◽  
Peripheral Plasma ◽  
Intravenous Insulin ◽  
Hepatic Glucose ◽  
Diabetic Dogs

We have utilized a previously described mathematical model to study glucose disposal in fed, conscious, ambulatory, diabetic dogs. The model was applied to estimate the daily disposition of ingested glucose in the periphery, liver, and urine following a regular mixed meal containing 130 g of carbohydrate. Experimental data was obtained from 11 pancreatectomized animals. Both the portal and peripheral routes were used for intravenous insulin infusion and the daily profiles of peripheral plasma glucose and insulin concentrations measured. Total calories in mixed meals derived from carbohydrates (37%), fat (30%), and protein (30%). When judged according to the root-mean-square differences, agreement was excellent between model-predicted and experimentally observed glucose as well as insulin concentrations. This agreement occurred whether or not, in addition to basal insulin, meal insulin was also given. Using the model, we then predicted in detail the rates of glucose uptake in peripheral tissue, liver, and kidneys. With portally infused insulin resulting in diurnal glycemic normalization, the net daily hepatic glucose balance was physiological, being close to zero. Remarkably, with peripheral insulin infusions there was an unphysiological net negative hepatic glucose balance of 10 g/day.

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