Korean Diabetes J.  2010 Feb;34(1):2-9. 10.4093/kdj.2010.34.1.2.

The Incretins and Pancreatic beta-Cells: Use of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide to Cure Type 2 Diabetes Mellitus

• Kim MH
• Lee MK

• KMID: 2298038
• DOI: http://doi.org/10.4093/kdj.2010.34.1.2

Abstract

Type 2 diabetes mellitus (T2DM) is increasing in prevalence worldwide. The complications associated with T2DM result in increased mortality and financial cost for those affected. T2DM has long been known to be associated with insulin resistance in peripheral tissues and a relative degree of insulin deficiency. However, the concept that insulin secretion and insulin sensitivity are not linked through a hyperbolic relationship in T2DM has continuously been demonstrated in many clinical trials. Thus, in order to prevent and treat T2DM, it is necessary to identify the substance(s) that will improve the function and survival of the pancreatic beta-cells in both normal and pathologic conditions, so that production and secretion of insulin can be enhanced. Incretin hormones, such as glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP), have been shown to lower the postprandial and fasting glucose and the glycated hemoglobin levels, suppress the elevated glucagon level, and stimulate glucose-dependent insulin synthesis and secretion. In this report, we will review the biological actions and mechanisms associated with the actions of incretin hormones, GLP-1 and GIP, on beta-cell health and compare the differences between GLP-1 and GIP.

Keyword

Glucose-dependent insulinotropic polypeptide; Glucagon-like peptide-1; Incretins; Diabetes Mellitus, Type 2

MeSH Terms

Diabetes Mellitus, Type 2
Fasting
Glucagon
Glucagon-Like Peptide 1
Glucose
Hemoglobins
Incretins
Insulin
Insulin Resistance
Prevalence
Glucagon
Glucagon-Like Peptide 1
Glucose
Hemoglobins
Incretins
Insulin

Figure

• 

  Fig. 1 Proposed model for action of Wnt signaling on GLP-1 or GIP production. Wnt ligands bind to Frizzled (Fz) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6 coreceptors, whereby dishevelled (Dsh) is recruited to the membrane and GSK3β is inhibited by the activation of Dsh by Fz. This leads to the translocation of β-catenin into the nucleus, where it binds with TCF to activate specific target genes such as GLP-1 and GIP in intestinal L-cells or K-cells. GLP-1, glucagon-like peptide-1; GIP, glucose-dependent insulinotropic polypeptide.

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