Abstract
Glucose metabolism is tightly controlled by multiple hormones and neurotransmitters in response to nutritional, environmental, and emotional changes. In addition to insulin and glucagon produced by pancreatic islets, two incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP, also known as glucose-dependent insulinotropic peptide), also play important roles in blood glucose homeostasis. The incretin hormones mainly exert their regulatory effects via their corresponding receptors, which are expressed in pancreatic islets as well as many other extra-pancreatic organs. Recent studies have shown that the genes which encode these two incretin hormones can be regulated by the effectors of the Wnt signaling pathway, including TCF7L2, a transcription factor identified recently by extensive genome wide association studies as an important type 2 diabetes risk gene. Interestingly, TCF7L2 and β-catenin (β-cat), another effector of Wnt signaling pathway, may also mediate the function of the incretin hormones as well as the expression of their receptors in pancreatic β-cells. In this review, we have introduced the incretin hormones and the Wnt signaling pathway, summarized recent findings in the field, and provided our perspectives.
Highlights
The metabolic syndrome is a multifactorial disease involving complex interactions between aging, genetics, behavior, and environment
The authors regret not being able to cite all of the excellent contributions in the field due to space limitations
Great insights could be gained through further studies on the beneficial versus deleterious effects of TCF7L2 alternatively spliced variants in different organs
Summary
The metabolic syndrome is a multifactorial disease involving complex interactions between aging, genetics, behavior, and environment. The studies on the expression and function of incretin hormones has enriched our understanding of the mechanisms underlying glucose and energy homeostasis, and have led to the development of two novel categories of therapeutic drugs for T2D and its complications.
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