Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles

Vella, Adrian; Reed, Ann S.; Charkoudian, Nisha; Shah, Pankaj; Basu, Rita; Basu, Ananda; Joyner, Michael J.; Rizza, Robert A.

doi:10.1152/ajpendo.00530.2002

Cited by 23 publications

(21 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, the rate of infusion of [6,6-2 H 2 ]glucose was altered to approximate the anticipated pattern of fall in EGP, thereby minimizing the change in plasma glucose enrichment. Blood was sampled from the arterialized venous site at Ϫ120, Ϫ30, Ϫ20, Ϫ10, 0, 5,10,15,20,30,40,50,60,75,90,120,150,180,210,240,260,280, 300, 360, and 420 min. Intravenous lines were then removed, and the subject ate lunch immediately after completion of the study (ϳ1600 -1700) and a supper at ϳ2000 -2030.…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, the liver was exposed to a relatively greater amount of insulin. This combined with the ability of hyperglycemia per se to inhibit hepatic glucose release (40) presumably resulted in normal postprandial suppression of EGP in the elderly men. Taken together, these data indicate that the greater postprandial rise in glucose concentrations in the elderly compared with young men was caused by lower rates of glucose disposal due to insulin resistance, impaired insulin secretion, and increased hepatic insulin extraction.…”

Section: Effects Of Age On Glucose Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Age and Sex on Postprandial Glucose Metabolism

et al. 2006

View full text Add to dashboard Cite

To determine the effects of age and sex on the regulation of postprandial glucose metabolism, glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction were concurrently measured in 145 healthy elderly (aged 70 ؎ 1 years) and in 58 young (aged 28 ؎ 1 years) men and women before and after ingestion of a mixed meal containing [1-13 C]glucose. At the time of meal ingestion, [6-3 H]glucose and [6,6-2 H 2 ]glucose were infused intravenously to enable concurrent measurement of the rates of postprandial endogenous glucose production (EGP), meal appearance, and glucose disappearance. Fasting and postprandial glucose concentrations were higher (P < 0.001) in both elderly women and elderly men compared with young individuals of the same sex. The higher postprandial glucose concentrations in the elderly than young women were caused by higher rates of meal appearance (P < 0.01) and slightly lower (P < 0.05) rates of glucose disappearance immediately after eating. In contrast, higher glucose concentrations in the elderly than young men were solely due to decreased (P < 0.001) glucose disappearance. Although postprandial glucose concentrations did not differ in elderly women and elderly men, rates of meal appearance and glucose disappearance rates both were higher (P < 0.001) in the women. Fasting EGP was higher (P < 0.05) in elderly than young subjects of both sexes and in women than men regardless of age. On the other hand, postprandial suppression of EGP was rapid all groups. Insulin action and secretion were lower (P < 0.001) in the elderly than young men but did not differ in the elderly and young women. This resulted in lower (P < 0.001) meal disposition indexes in elderly than young men but no difference in elderly and young women. Total meal disposition indexes were lower (P < 0.05) in elderly men than elderly women, indicating impaired insulin secretion, whereas disposition indexes were higher (P < 0.05) in young men than young women. Hepatic insulin clearance was greater (P < 0.001) in the elderly than young subjects of both sexes but did not differ between men and women regardless of age. In contrast, the ability of glucose to facilitate its own uptake (glucose effectiveness) was higher (P < 0.001) in women than men but did not differ in elderly and young subjects. Thus, age and sex impact on insulin secretion, insulin action, hepatic insulin extraction, and glucose effectiveness, resulting in substantial differences in the regulation of postprandial glucose metabolism in men and women and in elderly and young subjects. Diabetes 55: [2001][2002][2003][2004][2005][2006][2007][2008][2009][2010][2011][2012][2013][2014] 2006 I t is well established that glucose tolerance decreases with age and that this decrease is commonly associated with impaired insulin secretion and action. However, most previous studies have measured insulin action during intravenous glucose or insulin administration, and many studies have measured plasma insulin concentrations rather than actual insulin secretion rate...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Effects Of Age On Glucose Metabolismmentioning

confidence: 99%

Effects of Age and Sex on Postprandial Glucose Metabolism

et al. 2006

View full text Add to dashboard Cite

show abstract

“…382 For the lower (5 g/0.5 U) and higher (20 g/2 U) dose variants, 383 EGP suppr was shifted to 0-50 and 50-100%, respectively. Stud-384 ies have shown a direct dose-dependent relationship between 385 glucose concentration and suppression of EGP [57], validating 386 this basic approach.…”

Section: Article In Pressmentioning

confidence: 85%

“…During this transient state, the 56 metabolic system model employed has been shown to be 57 highly correlated (r = 0.97) to the clamp test [22,23] …”

mentioning

confidence: 99%

Monte Carlo analysis of a new model-based method for insulin sensitivity testing

Lotz

Chase

McAuley

et al. 2008

Computer Methods and Programs in Biomedicine

144

View full text Add to dashboard Cite

show abstract

“…Insulin and hyperglycemia inhibit whereas glucagon stimulates EGP (32,48). Hence, the portal venous insulin-to-glucagon ratio is a major determinant of EGP (32).…”

Section: Discussionmentioning

confidence: 99%

Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments

Mallad

Man

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments. Am J Physiol Endocrinol Metab 309: E474 -E486, 2015. First published July 7, 2015; doi:10.1152/ajpendo.00236.2015.-Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon's effects on EGP was used to develop an in silico glucagon action model. The model-derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia. glucagon; type 1 diabetes; endogenous glucose production A CUTTING-EDGE ARTIFICIAL PANCREAS (AP) system applied in type 1 diabetes (T1D) needs to prevent and treat hypoglycemia. This is a critical goal determined by the Food and Drug Administration in their recent guidance document for an AP system (50). To meet this goal, the main counterregulatory hormone glucagon may be utilized not only to "rescue" from but also to prevent hypoglycemia. Glucagon acutely stimulates hepatic glycogenolysis and thereby endogenous glucose production (EGP) (11-13, 32). However, although the dose response of glucagon on EGP (viz., hepatic glucagon sensitivity) in T1D is currently unknown during hypoglycemia, a recent study (20) did demonstrate a dose response at euglycemia that was modulated by prevailing insulin concentrations. Furthermore, whether this is contingent on prevailing glucose concentrations and whether glucagon clearance is influenced by changing glucagon concentrations are also undetermined. Filling such knowledge gaps in glucagon physiology are vital to inform and design a control algorithm where the intensity of the "controller" can be modulated based on the information obtained. For example, if hepatic glucagon sensitivity increases with hypoglycemia, a lesser dose of glucagon could evoke an equivalent glucose response than at euglycemia. On the other hand, if hepatic glucagon sensitivity does not alter with glucose levels, then th...

show abstract

Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles

Cited by 23 publications

References 34 publications

Effects of Age and Sex on Postprandial Glucose Metabolism

Effects of Age and Sex on Postprandial Glucose Metabolism

Monte Carlo analysis of a new model-based method for insulin sensitivity testing

Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments

Contact Info

Product

Resources

About