From the Guidelines
Glucose-dependent insulinotropic polypeptide (GIP) plays a crucial role in regulating blood glucose levels and metabolism, primarily through stimulating insulin secretion from pancreatic beta cells in a glucose-dependent manner, as supported by recent guidelines 1. GIP is primarily released from K cells in the upper small intestine in response to nutrient intake, particularly fats and carbohydrates. Its main function is to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner, meaning it only enhances insulin release when blood glucose levels are elevated. This glucose dependency is important as it prevents hypoglycemia. Beyond insulin secretion, GIP promotes beta cell proliferation and survival, helping maintain pancreatic function over time. It also influences fat metabolism by enhancing fat storage in adipose tissue and reducing fat breakdown. In the brain, GIP affects appetite regulation and cognitive function. Some key points about GIP function include:
- Stimulation of insulin secretion in a glucose-dependent manner
- Promotion of beta cell proliferation and survival
- Influence on fat metabolism
- Effects on appetite regulation and cognitive function In individuals with type 2 diabetes, there is often a reduced insulinotropic effect of GIP, contributing to impaired insulin secretion. This understanding has led to the development of GIP-based therapies, including dual GIP/GLP-1 receptor agonists, which are showing promise in diabetes treatment by improving glycemic control and supporting weight loss through their combined metabolic effects, as recommended in recent standards of care 1.
From the Research
Role of GIP
- GIP, or glucose-dependent insulinotropic polypeptide, is an incretin hormone that plays a crucial role in regulating insulin and glucagon secretion in the body 2, 3, 4.
- GIP is secreted by enteroendocrine cells in the intestinal mucosa in response to nutrient ingestion and enhances insulin secretion in a glucose-dependent manner 3, 4.
- The effects of GIP on insulin and glucagon secretion are highly dependent on the blood glucose levels, with GIP increasing glucagon at fasting glycaemia and lower levels of glycaemia, and increasing insulin release at hyperglycaemia 4.
Function of GIP
- GIP has additive effects on insulin secretion with another incretin hormone, GLP-1 (glucagon-like peptide-1) 3.
- GIP increases triglyceride storage in white adipose tissue, not only through stimulating insulin secretion but also by interacting with regional blood vessels and GIP receptors 3.
- GIP plays a role in bone remodeling, and has beneficial effects on cardiovascular complications and neurodegenerative central nervous system (CNS) disorders 3.
- GIP receptor co-agonists, such as tirzepatide, have superior efficacy compared to selective GLP-1 receptor agonists with respect to glycaemic control and body weight, renewing interest in GIP as a therapeutic target 3.
GIP and Glucagon Secretion
- GIP increases glucagon secretion at fasting glycaemia and lower levels of glycaemia, while decreasing glucagon secretion at hyperglycaemia 4.
- The regulation of glucagon secretion by GIP is important, as the combination of inadequate insulin secretion and excessive glucagon secretion contribute to hyperglycaemia in patients with type 2 diabetes 4.
- GIP may also have a role in preventing hypoglycaemia in patients with type 1 diabetes by increasing glucagon release and augmenting endogenous glucose production 4.