Summary
Glucagon-like peptide 1 (GLP-1) (7-36 amide) is a physiological incretin hormone that is released after nutrient intake from the lower gut and stimulates insulin secretion at elevated plasma glucose concentrations. Previous work has shown that even in Type 2 (non-insulin-dependent) diabetic patients GLP-1 (7-36 amide) retains much of its insulinotropic action. However, it is not known whether the magnitude of this response is sufficient to normalize plasma glucose in Type 2 diabetic patients with poor metabolic control. Therefore, in 10 Type 2 diabetic patients with unsatisfactory metabolic control (HbAlc 11.6±1.7%) on diet and sulphonylurea therapy (in some patients supplemented by metformin or acarbose), 1.2 pmol ×kg−1×min−1 GLP-1 (7-36 amide) or placebo was infused intravenously in the fasting state (plasma glucose 13.1±0.6 mmol/l). In all patients, insulin (by 17.4±4.7 nmol ×1−1×min; p=0.0157) and C-peptide (by 228.0±39.1 nmol×1−1×min; p=0.0019) increased significantly over basal levels, glucagon was reduced (by -1418±308 pmol ×1−1×min) and plasma glucose reached normal fasting concentrations (4.9±0.3 mmol/l) within 4 h of GLP-1 (7-36 amide) administration, but not with placebo. When normal fasting plasma glucose concentrations were reached insulin returned towards basal levels and plasma glucose concentrations remained stable despite the ongoing infusion of GLP-1 (7-36 amide). Therefore, exogenous GLP-1 (7-36 amide) is an effective means of normalizing fasting plasma glucose concentrations in poorly-controlled Type 2 diabetic patients. The glucose-dependence of insulinotropic actions of GLP-1 (7-36 amide) appears to be retained in such patients.
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Eissele R, Göke R, Willemer S et al. (1992) Glucagon-like peptide 1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22: 283–291
Kreymann B, Ghatei MA, Williams G, Bloom SR (1987) Glucagon-like peptide 1 7–36: a physiological incretin in man. Lancet II: 1300–1304
Nauck M, Bartels E, Ørskov C, Ebert R, Creutzfeldt W (1993) Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 (7-36 amide) infused at near-physiological insulinotropic hormone and glucose concentrations. J Clin Endocrinol Metab 76: 912–917
Nauck MA, Heimesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt W (1993) Preserved incretin activity of glucagon-like peptide 1 (GLP-1) (7-36 amide) but not of synthetic human gastric inhibitory polypeptide (GIP) in patients with Type 2 diabetes mellitus. J Clin Invest 91: 301–307
Nathan DM, Schreiber E, Fogel H, Mojsov S, Habener JF (1992) Insulinotropic action of glucagon-like peptide-I-(7-36) in diabetic and nondiabetic subjects. Diabetes Care 15: 270–276
Gutniak M, Ørskov C, Holst JJ, Ahren B, Efendic S (1992) Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes. N Engl J Med 326: 1316–1322
Wettergen A, Scholdager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ (1990) Truncated GLP-1 (proglucagon 87-107 amide) from distal gut: role in regulation of gastric and pancreatic functions. Digestion 46 [Suppl 1]: 120 (Abstract)
Ørskov C, Holst JJ (1987) Radio-immunoassays for glucagonlike peptides 1 and 2 (GLP-1 and GLP-2). Scand J Clin Lab Invest 47: 165–174
Holst JJ (1982) Evidence that peak II GLI or enteroglucagon is identical to the C-terminal sequence (residues 33-69) of glicentin. Biochem J 207: 381–388
Polonsky KS, Given BD, Hirsch LJ et al. (1988) Abnormal patterns of insulin secretion in noninsulin-dependent diabetes mellitus. N Engl J Med 318: 1231–1239
Ørskov C, Holst JJ, Nielsen OV (1988) Effect of glucagon-like peptide 1 (proglucagon (78-107) amide) on endocrine secretion from pig pancreas, antrum and nonantral stomach. Endocrinology 123: 2009–2013
Komatsu R, Matsuyama T, Namba M et al. (1989) Glucagonostatic and insulinotropic action of glucagonlike peptide 1-(7-36)amide. Diabetes 38: 902–905
Ørskov C (1992) Glucagon-like peptide-1, a new hormone of the entero-insular axis. Diabetologia 35: 701–711
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Nauck, M.A., Kleine, N., Ørskov, C. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in Type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741–744 (1993). https://doi.org/10.1007/BF00401145
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DOI: https://doi.org/10.1007/BF00401145