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Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients.
Diabetologia. 2002 Aug; 45(8):1111-9.D

Abstract

AIMS/HYPOTHESIS

Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose-dependent insulinotropic polypeptide (GIP) is less effective. Our investigation evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C-peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes.

METHODS

Protocol 1: eight Type II diabetic patients and eight matched healthy subjects received i.v. bolus injections of GLP-1(2.5 nmol) or GIP(7.5 nmol) concomitant with an increase of plasma glucose to 15 mmol/l. Protocol 2: eight Type II diabetic patients underwent a hyperglycaemic clamp (15 mmol/l) with infusion (per kg body weight/min) of either: 1 pmol GLP-1 (7-36) amide (n=8), 4 pmol GIP (n=8), 16 pmol GIP (n=4) or no incretin hormone (n=5). For comparison, six matched healthy subjects were examined.

RESULTS

Protocol 1: Type II diabetic patients were characterised by a decreased "early phase" response to both stimuli, but their relative response to GIP versus GLP-1 stimulation was exactly the same as in healthy subjects [insulin (C-peptide): patients 59+/-9% (74+/-6%) and healthy subjects 62+/-5% (71+/-9%)]. Protocol 2, "Early phase" (0-20 min) insulin response to glucose was delayed and reduced in the patients, but enhanced slightly and similarly by GIP and GLP-1. GLP-1 augmented the "late phase" (20-120 min) insulin secretion to levels similar to those observed in healthy subjects. In contrast, the "late phase" responses to both doses of GIP were not different from those obtained with glucose alone. Accordingly, glucose infusion rates required to maintain the hyperglycaemic clamp in the "late phase" period (20-120 min) were similar with glucose alone and glucose plus GIP, whereas a doubling of the infusion rate was required during GLP-1 stimulation.

CONCLUSION/INTERPRETATION

Lack of GIP amplification of the late phase insulin response to glucose, which contrasts markedly to the normalising effect of GLP-1, could be a key defect in insulin secretion in Type II diabetic patients.

Authors+Show Affiliations

Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark. tivi@gentoftehosp.kbhamt.dkNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12189441

Citation

Vilsbøll, T, et al. "Defective Amplification of the Late Phase Insulin Response to Glucose By GIP in Obese Type II Diabetic Patients." Diabetologia, vol. 45, no. 8, 2002, pp. 1111-9.
Vilsbøll T, Krarup T, Madsbad S, et al. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia. 2002;45(8):1111-9.
Vilsbøll, T., Krarup, T., Madsbad, S., & Holst, J. J. (2002). Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia, 45(8), 1111-9.
Vilsbøll T, et al. Defective Amplification of the Late Phase Insulin Response to Glucose By GIP in Obese Type II Diabetic Patients. Diabetologia. 2002;45(8):1111-9. PubMed PMID: 12189441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. AU - Vilsbøll,T, AU - Krarup,T, AU - Madsbad,S, AU - Holst,J J, Y1 - 2002/07/04/ PY - 2001/10/08/received PY - 2002/02/25/revised PY - 2002/8/22/pubmed PY - 2003/2/26/medline PY - 2002/8/22/entrez SP - 1111 EP - 9 JF - Diabetologia JO - Diabetologia VL - 45 IS - 8 N2 - AIMS/HYPOTHESIS: Glucagon-like-peptide-1 (GLP-1) is strongly insulinotropic in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas glucose-dependent insulinotropic polypeptide (GIP) is less effective. Our investigation evaluated "early" (protocol 1) - and "late phase" (protocol 2) insulin and C-peptide responses to GLP-1 and GIP stimulation in patients with Type II diabetes. METHODS: Protocol 1: eight Type II diabetic patients and eight matched healthy subjects received i.v. bolus injections of GLP-1(2.5 nmol) or GIP(7.5 nmol) concomitant with an increase of plasma glucose to 15 mmol/l. Protocol 2: eight Type II diabetic patients underwent a hyperglycaemic clamp (15 mmol/l) with infusion (per kg body weight/min) of either: 1 pmol GLP-1 (7-36) amide (n=8), 4 pmol GIP (n=8), 16 pmol GIP (n=4) or no incretin hormone (n=5). For comparison, six matched healthy subjects were examined. RESULTS: Protocol 1: Type II diabetic patients were characterised by a decreased "early phase" response to both stimuli, but their relative response to GIP versus GLP-1 stimulation was exactly the same as in healthy subjects [insulin (C-peptide): patients 59+/-9% (74+/-6%) and healthy subjects 62+/-5% (71+/-9%)]. Protocol 2, "Early phase" (0-20 min) insulin response to glucose was delayed and reduced in the patients, but enhanced slightly and similarly by GIP and GLP-1. GLP-1 augmented the "late phase" (20-120 min) insulin secretion to levels similar to those observed in healthy subjects. In contrast, the "late phase" responses to both doses of GIP were not different from those obtained with glucose alone. Accordingly, glucose infusion rates required to maintain the hyperglycaemic clamp in the "late phase" period (20-120 min) were similar with glucose alone and glucose plus GIP, whereas a doubling of the infusion rate was required during GLP-1 stimulation. CONCLUSION/INTERPRETATION: Lack of GIP amplification of the late phase insulin response to glucose, which contrasts markedly to the normalising effect of GLP-1, could be a key defect in insulin secretion in Type II diabetic patients. SN - 0012-186X UR - https://www.unboundmedicine.com/medline/citation/12189441/Defective_amplification_of_the_late_phase_insulin_response_to_glucose_by_GIP_in_obese_Type_II_diabetic_patients_ L2 - https://doi.org/10.1007/s00125-002-0878-6 DB - PRIME DP - Unbound Medicine ER -