Defective regulation of phosphatidylinositol-3-kinase gene expression in skeletal muscle and adipose tissue of non-insulin-dependent diabetes mellitus patients
Open accessAbstract
We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85alpha-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. The in vivo regulation by insulin was studied using a 3-h euglycaemic, hyperinsulinaemic clamp. There were no differences in the basal concentrations of the three mRNAs in skeletal muscle between groups. Insulin infusion produced a twofold reduction in insulin receptor substrate-1 mRNA expression in the three groups (p<0.02). In contrast, insulin increased p85alpha-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects (+98+/-22% in lean and +127+/-16% in obese, p<0.02) but this effect was totally impaired in Type II diabetic patients (+5+/-12%, NS). A similar defect in insulin action on p85alpha-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue (+138+/-25%, p<0.01 in lean and +46+/-14%, p<0.02 in obese and +29+/-11%, NS in Type II diabetic patients). The lack of action of insulin on p85alpha-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes.
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Obese human subjects were normoglycemic and hyperinsulinemic and showed 50% lower insulin-stimulated glucose disposal than lean subjects, as assessed by euglycemic-hyperinsulinemic clamp (4.9 ± 0.8 vs 10.1 ± 1.1 mg/kg/min).
“Obese subjects were normoglycemic and hyperinsulinemic and showed 507 lower insulin-stimulated glucose disposal as assessed by euglycemic-hyperinsulinemic clamp (4.9 + 0.8 and 10.1 + 1.1 mg/kg/min for obese and lean subjects, respectively) (27”
From Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism (2003) · cites this paper as [27]
The Comparison of insulin-resistant patients and control subjects section reports higher fasting insulin in obese subjects than in lean subjects and markedly reduced insulin-stimulated glucose uptake during a hyperinsulinaemic clamp. Table 1 shows similar fasting glycaemia in the two groups. It reports uptake in different units (1126 ± 147 versus 1991 ± 156 mmol/m²/min), however, and does not support the claimed values of 4.9 ± 0.8 versus 10.1 ± 1.1 mg/kg/min. (LLM, conf=0.88)
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- Authors
- Andreelli, F., Laville, M., Ducluzeau, P.-H., Vega, N., Vallier, P., Khalfallah, Y., Riou, J.-P., & Vidal, H.
- Affiliations
- Inserm (FR)
- Venue
- Diabetologia
- Published
- 1999-02-19
- Volume
- 42
- Issue
- 3
- Pages
- 358-364
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2003727862
- Cited by
- 60
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2021: 3 · 2018: 3 · 2017: 2 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Fondation de France
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- type 2 diabetes, insulin resistance, phosphatidylinositol 3-kinase, IRS-1, insulin receptor, gene expression regulation, skeletal muscle, adipose tissue, obesity, hyperinsulinemic-euglycemic clamp, insulin action
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Infusions, Intravenous, Insulin, Male, Middle Aged, Obesity, Reference Values, RNA, Messenger, Transcription, Genetic, Glucose Clamp Technique, Gene Expression Regulation, Enzymologic, Muscle, Skeletal, Phosphatidylinositol 3-Kinases
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