Until the causes of diabetic complications are known, presumably therapy should attempt to normalize glucose metabolism as well as glucose concentration. This requires an understanding of how glucose, insulin, and glucagon interact to regulate glucose metabolism in nondiabetic humans and how these interactions are influenced by NIDDM. The investigators will examine these questions by first testing the hypothesis that short term (overnight) changes in glycemic control alters insulin action and glucose effectiveness (i.e. the ability of glucose to stimulate its own uptake and to suppress its own release) in people with NIDDM. Having defined the conditions of study, the investigators will then examine the assumptions of several widely used models of glucose metabolism (e.g. the """"""""cold"""""""" and """"""""hot"""""""" minimal models). The investigators will determine whether, in the presence of """"""""basal"""""""" insulin concentrations, increases in glucose concentration within the physiologic range result in linear suppression of hepatic glucose release and linear stimulation of disposal, whether NIDDM alters this relationship, whether hyperglycemia alters the kinetic as well as well as the absolute response to insulin, and whether NIDDM alters the inhibitory effects of glucose on its own clearance. The investigators also will use the triple tracer technique to examine the mechanism(s) by which glucose facilitates its own uptake in nondiabetic humans and to determine whether NIDDM alters glucose induced stimulation of transport and/or phosphorylation in muscle. The investigators will simultaneously use splanchnic catheterization to establish the contribution of splanchnic and extrasplanchnic tissues to glucose uptake and to test the hypothesis that NIDDM impairs glucose induced stimulation of glucose uptake in the splanchnic bed. The investigators will explore the interactions between insulin and glucagon by determining whether NIDDM alters the hepatic response to glucagon and by testing the hypotheses that lack of suppression of glucagon exacerbates hyperglycemia in people with NIDDM when insulin secretion is delayed and decreased but not when there is a rapid increase in insulin as occurs in nondiabetic humans after food ingestion. Finally, the investigators will determine whether the novel therapeutic agent GLP-1, in addition to increasing insulin secretion and suppression of glucagon, also improves insulin action and glucose effectiveness in people with NIDDM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK029953-19
Application #
6177318
Study Section
Metabolism Study Section (MET)
Program Officer
Laughlin, Maren R
Project Start
1982-05-01
Project End
2001-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
19
Fiscal Year
2000
Total Cost
$351,045
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Rizza, Robert A; Toffolo, Gianna; Cobelli, Claudio (2016) Accurate Measurement of Postprandial Glucose Turnover: Why Is It Difficult and How Can It Be Done (Relatively) Simply? Diabetes 65:1133-45
Basu, Ananda; Veettil, Sona; Dyer, Roy et al. (2016) Direct Evidence of Acetaminophen Interference with Subcutaneous Glucose Sensing in Humans: A Pilot Study. Diabetes Technol Ther 18 Suppl 2:S243-7
Schiavon, Michele; Dalla Man, Chiara; Dube, Simmi et al. (2015) Modeling Plasma-to-Interstitium Glucose Kinetics from Multitracer Plasma and Microdialysis Data. Diabetes Technol Ther 17:825-31
Limberg, Jacqueline K; Taylor, Jennifer L; Mozer, Michael T et al. (2015) Effect of bilateral carotid body resection on cardiac baroreflex control of blood pressure during hypoglycemia. Hypertension 65:1365-71
Basu, Ananda; Dube, Simmi; Veettil, Sona et al. (2015) Time lag of glucose from intravascular to interstitial compartment in type 1 diabetes. J Diabetes Sci Technol 9:63-8
Wehrwein, Erica A; Limberg, Jacqueline K; Taylor, Jennifer L et al. (2015) Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans. Exp Physiol 100:69-78
Limberg, Jacqueline K; Dube, Simmi; Kuijpers, Myrthe et al. (2015) Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus. Clin Auton Res 25:243-50
Visentin, Roberto; Dalla Man, Chiara; Basu, Rita et al. (2015) Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to a single-tracer oral minimal model. Am J Physiol Endocrinol Metab 309:E161-7
Limberg, Jacqueline K; Farni, Kathryn E; Taylor, Jennifer L et al. (2014) Autonomic control during acute hypoglycemia in type 1 diabetes mellitus. Clin Auton Res 24:275-83
Limberg, Jacqueline K; Taylor, Jennifer L; Dube, Simmi et al. (2014) Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans. Exp Physiol 99:640-50

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