L’insulinorésistance commence à se développer aux stades précoces du diabète de type 2.9

Les cellules β essayent de réguler mais finalement elles  ne peuvent pas compenser l’insulinorésistance, entrainant une élévation de la glycémie.9

En parallèle, la réponse incrétine diminue (incluant la réponse au GLP-1), contribuant ainsi à l’incapacité croissante des cellules β à sécréter de l’insuline.3,10

En plus d’autres facteurs, l’activité insuffisante du GLP-1 entraîne une diminution de la sécrétion d’insuline et de l’inhibition de la sécrétion de glucagon.3

1.

Høiberg PV. Vilsbøll T, Rabol R. et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 2009;52:199-207.

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Kjems LL. Holst JL Vølund A. Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003;52:380-386.

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Calanna S. Christensen M, Holst D, et al. Secretion of glucagon.like peptide. 1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia. 2013;56:965-972.

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Aronoff SL, Berkowitz K. Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum. 2004;17:183-190.

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Halbirk M et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-I infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol. 2010;298: H1096—H1102.

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Korner M. Stockli M. Waser B. Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting.   J Nucl Med. 2007;48:736-743

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DeFronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment Of type 2 diabetes mellitus. Diabetes. 2009;58:773-795.

8.

Holst JJ, Knop FK. Vilsbøll T, Krarup T, Madsbad S. Loss of incretin effect is a specific. important, and early characteristic of type 2 diabetes, Diabetes Care. 2011;35(suppl 2):S251-S257.

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Leahy JL. Pathogenesis of type 2 diabetes. Arch Med Res. 2005;36:197-209.

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Herzberg.Schäfer S. Heni M, Stefan N, Haring H-u, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab. 2012; 14(suppl 3):85-90.

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Nauck MA, Meier JJ. GIP and GLP-1: stepsiblings rather than monozygotic twins within the incretin family. Diabetes. 2019;68:897-900.

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LeRoith D. Beta-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities. Am J Med. 2002. PMID: 12431757 Review.