GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and ␣-glucosidase
Normalization of fasting glycaemia by intravenous GLP-1 ([7-36 amide] or [7-37]) in Type 2 diabetic patients
✍ Scribed by Nauck, M.A.; Weber, I.; Bach, I.; Richter, S.; Ørskov, C.; Holst, J.J.; Schmiegel, W.
- Book ID
- 101218268
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 185 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0742-3071
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✦ Synopsis
Intravenous GLP-1 [7-36 amide] can normalize fasting hyperglycaemia in Type 2 diabetic patients. Whether GLP-1 [7-37] has similar effects and how quickly plasma glucose concentrations revert to hyperglycaemia after stopping GLP-1 is not known. Therefore, 8 patients with Type 2 diabetes (5 female, 3 male; 65 ؎ 6 years; BMI 34.3 ؎ 7.9 kg m -2 ; HbA 1c 9.6 ؎ 1.2 %; treatment with diet alone (n = 2), sulphonylurea (n = 5), metformin (n = 1)) were examined twice in randomized order. GLP-1 [7-36 amide] or [7-37] (1 pmol kg -1 min -1 ) were infused intravenously over 4 h in fasted subjects. Plasma glucose (glucoseoxidase), insulin and C-peptide (ELISA) was measured during infusion and for 4 h thereafter. Indirect calorimetry was performed. Fasting hyperglycaemia was 11.7 ؎ 0.9 [7-36 amide] and 11.3 ؎ 0.9 mmol l -1 [7-37]. GLP-1 infusions stimulated insulin secretion approximately 3-fold (insulin peak 168 ؎ 32 and 156 ؎ 47 pmol l -1 , p Ͻ 0.0001 vs basal; C-peptide peak 2.32 ؎ 0.28 and 2.34 ؎ 0.43 nmol l -1 , p Ͻ 0.0001, respectively, with GLP-1 [7-36 amide] and [7-37]). Four hours of GLP-1 infusion reduced plasma glucose (4.8 ؎ 0.4 and 4.6 ؎ 0.3 mmol l -1 , p Ͻ 0.0001 vs basal values), and it remained in the non-diabetic fasting range after a further 4 h (5.1 ؎ 0.4 and 5.3 ؎ 0.4 mmol l -1 , for GLP [7-36 amide] and [7-37], respectively). There were no significant differences between GLP-1 [7-36 amide] and [7-37] (glucose, p = 0.99; insulin, p = 0.99; C-peptide, p = 0.99). Neither glucose oxidation nor lipid oxidation (or any other parameters determined by indirect calorimetry) changed during or after the administration of exogenous GLP-1. In conclusion, GLP-1 [7-36 amide] and [7-37] normalize fasting hyperglycaemia in Type 2 diabetic patients. Diabetes therapy (diet, sulphonyl ureas or metformin) does not appear to influence this effect. In fasting and resting patients, the effect persists during administration of GLP-1 and for at least 4 h thereafter, without rebound. Significant changes in circulating substrate concentrations (e.g. glucose) are not accompanied by changes in intracellular substrate metabolism.
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