What is glucose-dependent insulinotropic polypeptide (GIP)?

Glucose-dependent insulinotropic polypeptide (GIP) is a hormone involved in the regulation of insulin secretion in response to food intake. This hormone is well reviewed by Baggio & Drucker (2007) who also juxtaposed it with GLP-1. 

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What Is GIP?

GIP is a peptide hormone produced by the K-cells located primarily in the duodenum and proximal jejunum (the upper part of the small intestine).

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Main Function

GIP is an incretin—a type of hormone that enhances the secretion of insulin from the pancreas in response to oral glucose (i.e., when you eat or drink something sugary).

• Stimulus for Release: Nutrient ingestion, especially glucose and fat, triggers GIP release.

• Action: Enhances insulin secretion from pancreatic beta cells, but only when blood glucose is elevated (hence, “glucose-dependent”).

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Key Roles of GIP

1. Insulin Secretion: Stimulates insulin release in a glucose-dependent manner.

2. Fat Metabolism: May promote lipid storage and fat metabolism in adipose tissue.

3. Bone Metabolism (emerging research): Some studies suggest GIP may influence bone remodeling.

4. Limited Effect on Gastric Motility: Unlike another incretin hormone, GLP-1 (glucagon-like peptide-1), GIP has minimal impact on slowing gastric emptying.

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Incretin Effect

GIP is one of the hormones responsible for the incretin effect—the phenomenon where oral glucose causes a much greater insulin response than intravenous glucose due to gut hormone action.

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Clinical Relevance

• In type 2 diabetes, the effectiveness of GIP is diminished—even though its secretion is often normal, the pancreatic response to GIP is reduced.

• GIP is being investigated as a target for new diabetes and obesity treatments. Some recent drugs (like tirzepatide) target both GIP and GLP-1 receptors for enhanced metabolic benefits.

How does GIP interacts with other hormones like GLP-1?

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are both incretin hormones—gut-derived hormones that help regulate insulin secretion after eating. While they share some similarities, they also have distinct roles and interactions. Here’s how they interact and complement each other:

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GIP and GLP-1: Similarities

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How GIP and GLP-1 Interact

1. Complementary Roles in Insulin Secretion

• Both amplify insulin secretion from pancreatic beta cells in the presence of elevated blood glucose.

• Together, they account for the “incretin effect”, where oral glucose triggers a stronger insulin response than intravenous glucose.

2. Differential Effects on Glucagon

• GIP may stimulate glucagon secretion during fasting or hypoglycemia, supporting blood sugar maintenance.

• GLP-1 inhibits glucagon during hyperglycemia, helping lower blood glucose further.

3. Different Effects on Gastric Emptying & Appetite

• GLP-1: Slows gastric emptying and suppresses appetite, contributing to weight loss.

• GIP: Has minimal effect on gastric emptying and appetite; may promote fat storage in adipose tissue.

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Therapeutic Synergy: GIP + GLP-1

Drugs that target both GIP and GLP-1 receptors (e.g., tirzepatide) show superior results for:

• Blood glucose lowering

• Weight loss

• Potential improvements in insulin sensitivity

Why this works!

• GLP-1 provides appetite control, reduced glucagon, and delayed gastric emptying.

• GIP enhances insulin secretion and may help restore beta-cell responsiveness over time. It is a target for therapies in the management of diabetes.

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