Insulin dose-response curves for stimulation of splanchnic glucose uptake and suppression of endogenous glucose production differ in nondiabetic humans and are abnormal in people with type 2 diabetes
Abstract
To determine whether the insulin dose-response curves for suppression of endogenous glucose production (EGP) and stimulation of splanchnic glucose uptake (SGU) differ in nondiabetic humans and are abnormal in type 2 diabetes, 14 nondiabetic and 12 diabetic subjects were studied. Glucose was clamped at approximately 9.5 mmol/l and endogenous hormone secretion inhibited by somatostatin, while glucagon and growth hormone were replaced by an exogenous infusion. Insulin was progressively increased from approximately 150 to approximately 350 and approximately 700 pmol/l by means of an exogenous insulin infusion, while EGP, SGU, and leg glucose uptake (LGU) were measured using the splanchnic and leg catheterization methods, combined with a [3-3H]glucose infusion. In nondiabetic subjects, an increase in insulin from approximately 150 to approximately 350 pmol/l resulted in maximal suppression of EGP, whereas SGU continued to increase (P < 0.001) when insulin was increased to approximately 700 pmol/l. In contrast, EGP progressively decreased (P < 0.001) and SGU progressively increased (P < 0.001) in the diabetic subjects as insulin increased from approximately 150 to approximately 700 pmol/l. Although EGP was higher (P < 0.01) in the diabetic than nondiabetic subjects only at the lowest insulin concentration, SGU was lower (P < 0.01) in the diabetic subjects at all insulin concentrations tested. On the other hand, in contrast to LGU and overall glucose disposal, the increment in SGU in response to both increments in insulin did not differ in the diabetic and nondiabetic subjects, implying a right shifted but parallel dose-response curve. These data indicate that the dose-response curves for suppression of glucose production and stimulation of glucose uptake differ in nondiabetic subjects and are abnormal in people with type 2 diabetes. Taken together, these data also suggest that agents that enhance SGU in diabetic patients (e.g. glucokinase activators) are likely to improve glucose tolerance.
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In other studies, S-free insulin concentrations have been comparable between type 2 diabetic patients and normal subjects.
“In other studies, S-free insulin concentrations have been comparable between type 2 diabetic patients and normal subjects.28,30 -32”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [31]
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Self-citation
- Authors
- Basu, R., Basu, A., Johnson, C. M., Schwenk, W. F., & Rizza, R. A.
- Affiliations
- Mayo Clinic (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-08-01
- Volume
- 53
- Issue
- 8
- Pages
- 2042-2050
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2150937124
- Cited by
- 97
- References
- 49
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 4 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- Novo Nordisk
- U.S. Public Health Service
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 29953)
- National Center for Research Resources (RR-00585, M01RR000585)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulin dose-response, endogenous glucose production, type 2 diabetes, glucose tolerance, glucokinase activators, hyperinsulinemic-euglycemic clamp, insulin resistance
- MeSH terms
- Biological Transport, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Glucagon, Glycolysis, Humans, Insulin, Kinetics, Reference Values, Splanchnic Circulation
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