Endocrinol Metab.  2023 Feb;38(1):1-9. 10.3803/EnM.2023.103.

Incretin and Pancreatic β-Cell Function in Patients with Type 2 Diabetes

• Ahn CH
• Oh TJ
• Min SH
• Cho YM

• KMID: 2539812
• DOI: http://doi.org/10.3803/EnM.2023.103

Abstract

To maintain normal glucose homeostasis after a meal, it is essential to secrete an adequate amount of insulin from pancreatic β-cells. However, if pancreatic β-cells solely depended on the blood glucose level for insulin secretion, a surge in blood glucose levels would be inevitable after the ingestion of a large amount of carbohydrates. To avoid a deluge of glucose in the bloodstream after a large carbohydrate- rich meal, enteroendocrine cells detect the amount of nutrient absorption from the gut lumen and secrete incretin hormones at scale. Since insulin secretion in response to incretin hormones occurs only in a hyperglycemic milieu, pancreatic β-cells can secrete a “Goldilocks” amount of insulin (i.e., not too much and not too little) to keep the blood glucose level in the normal range. In this regard, pancreatic β-cell sensitivity to glucose and incretin hormones is crucial for maintaining normal glucose homeostasis. In this Namgok lecture 2022, we review the effects of current anti-diabetic medications on pancreatic β-cell sensitivity to glucose and incretin hormones.

Keyword

Incretins; Insulin-secreting cells; Glucagon-like peptide 1; Glucose-dependent insulinotropic polypeptide; Diabetes mellitus, type 2

Figure

• 

  Fig. 1. In vivo assessment of β-cell glucose sensitivity using a graded insulin infusion protocol. (A) Estimation of β-cell glucose sensitivity by calculating the slope of the insulin secretion rate versus the blood glucose level. (B) Results showing that a single injection of liraglutide restored β-cell glucose sensitivity in patients with type 2 diabetes. Open triangles represent healthy control subjects. Open and closed rectangles represent type 2 diabetes subjects who received placebo or liraglutide, respectively. Adapted from Chang et al. [8], with permission from the American Diabetes Association. ISR, insulin secretion rate.

• 

  Fig. 2. In vivo assessment of β-cell incretin sensitivity using a hyperglycemic clamp with glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) infusion. (A) C-peptide responses to hyperglycemia, GLP-1 infusion, and GIP infusion in subjects with normal glucose tolerance and type 2 diabetes. (B) C-peptide response to hyperglycemia, GLP-1 infusion, and GIP infusion in subjects with type 2 diabetes before and after dapagliflozin treatment (magnified from Fig. 2A). Adapted from Ahn et al. NGT, normal glucose tolerance. aP<0.05 for comparison between NGT and predapagliflozin studies; bP<0.05 for comparison between NGT and both pre- and postdapagliflozin studies.

• 

  Fig. 3. A proposed mechanism explaining how anti-diabetic medications improve β-cell incretin sensitivity. Anti-diabetic medications including insulin, sulfonylurea, metformin, dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter 2 (SGLT2) inhibitor restores pancreatic β-cell glucose and incretin sensitivity by ameliorating hyperglycemia. GIPR, glucose-dependent insulinotropic polypeptide receptor; GLP-1R, glucagon-like peptide-1 receptor; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1.

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