The Enteric Enhancement of Glucose-stimulated Insulin Release: The Role of GIP in Aging, Obesity, and Non-insulin-dependent Diabetes Mellitus
Abstract
The effect of aging, obesity, and non-insulin-dependent diabetes mellitus on glucose-stimulated gastric inhibitory polypeptide (GIP) levels was studied in 55 male subjects, ranging in age from 19 to 84 yr, and in obesity, expressed as body mass index, from 21 to 34. Studies were performed using the hyperglycemie glucose clamp technique, in which the blood glucose was maintained at 125 mg/dl above basal for 2 h. Glucose (40 g/m2 body surface) was ingested at 60 min. Plasma immunoreactive GIP (IR-GIP) did not change during intravenous (i.v.) glucose alone, but began to rise within 10 min after glucose ingestion and reached a peak at 30–40 min. Basal and stimulated IR-GIP levels were markedly elevated in diabetic subjects and modestly elevated in obese subjects, compared with appropriately matched controls. In contrast, age had little effect on plasma IR-GIP levels either in the basal state or after glucose ingestion. When IR-GIP responses to oral glucose were expressed as a relative change from basal levels, IR-GIP rose 86% in diabetic subjects and 243% in obese subjects, compared with 185% and 165% in their respective controls. IR-GIP rose 179% in young subjects and 144% in middle-aged subjects, while, in old subjects, the increase was 265%. Plasma IRI levels were reduced in the diabetic subjects, slightly elevated in obese subjects, and were similar in older and younger subjects. Beta cell sensitivity to endogenous GIP decreases with age, and is unchanged in both obesity and nonmedicated diabetes.
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The use of a hyperglycemic clamp allows the determination of first-phase insulin secretion, which has utility in studies of subjects with diabetes.
“In addition, the use of a hyperglycemic clamp allows the determination of first-phase insulin secretion (23), which has utility in studies of subjects with diabetes.”
From Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods (2023) · cites this paper as [23]
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“comparable between young and old individuals, indicating that β-cell sensitivity to GIP is reduced in advancing age.(94)”
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“In obesity, GIP concentrations do not differ from HC [53, 54], while findings for GLP-1 remain inconclusive [55–58].”
- Authors
- Elahi, D., Andersen, D. K., Muller, D. C., Tobin, J. D., Brown, J. C., & Andres, R.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Brown, John C
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1984-10-01
- Volume
- 33
- Issue
- 10
- Pages
- 950-957
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2062195508
- Cited by
- 87
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2014: 7 · 2013: 1 · 2012: 3
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation pour la Recherche Médicale
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucose-dependent insulinotropic polypeptide, glucose-stimulated insulin secretion, aging, obesity, type 2 diabetes, oral glucose tolerance
- MeSH terms
- Insulin Secretion, Adult, Aged, Aging, Blood Glucose, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Gastrointestinal Hormones, Glucose, Humans, Hyperglycemia, Insulin, Islets of Langerhans, Male, Middle Aged, Obesity
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