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The Role of GIP in the Regulation of GLP-1 Satiety and Nausea

GIP is a hormone released from the enteroendocrine cells in the small intestine early during meal ingestion. Together with GLP-1, these two incretin hormones serve an important role in priming the β-cells of the pancreas to augment insulin secretion to regulate postprandial glucose levels. While pharmacotherapies targeting the GLP-1 system have been widely successful for the treatment of type 2 diabetes (T2D) and obesity, the use of GIP analogs as monotherapies has been largely underwhelming in preclinical and clinical studies and even produced some controversial findings. As such, GIP analogs were initially not pursued as monotherapies to treat diabetes or obesity due to the perception of…

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 How May GIP Enhance the Therapeutic Efficacy of GLP-1?

Although the therapeutic implications of the lipogenic actions of GIP are debated, its ability to improve lipid and glucose metabolism is especially evident when paired with the anorexigenic mechanism of GLP-1. We review the complexity of GIP in regulating adipose tissue function and energy balance in the context of recent findings in T2DM showing that dual GIP/GLP-1 receptor agonist therapy produces profound weight loss, glycemic control, and lipid lowering.

 Understanding the Role of GIP in Managing Diabetes and Obesity

Obesity and type 2 diabetes are two closely interconnected health challenges that are on the rise globally. Recent breakthroughs in the treatment were pioneered by Helmholtz Munich scientists and led to the development of so-called GIPR:GLP-1R co-agonists. These are compounds designed to target two specific hormone receptors in the human body: glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R). The receptors are involved in regulating glucose metabolism and insulin secretion and their pharmacological targeting promotes weight loss and reduction in food intake. However, the exact mechanisms and specific neuronal populations through which the hormone glucose-dependent insulinotropic polypeptide (GIP) affects energy balance and food intake remained so far largely elusive.

Articles of Interest

GIP and GLP‐1, the two incretin hormones: Similarities and differences

Gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the two primary incretin hormones secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. GIP and GLP‐1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP‐1 receptor (GLP‐1R), which belong to the G‐protein coupled receptor family.

GIP hormone: How it works for weight loss

The GIP hormone was originally discovered as a peptide that could inhibit gastric acid secretion and protect the small intestine from acid damage. This explains its original name: gastric inhibitory polypeptide (or gastric inhibitory peptide). Since then, it's been discovered that another hormone, secretin, is responsible for decreasing the production of stomach acid and that GIP actually plays a role in insulin secretion. For this reason, researchers changed the name of the hormone to glucose-dependent insulinotropic polypeptide (or glucose-dependent insulinotropic peptide) but maintained its original acronym, GIP.

The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have their main physiological role in augmenting insulin secretion after their nutrient-induced secretion from the gut. A functioning entero-insular (gut-endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance.

What Are GIP Receptor Agonists?

Glucose-dependent insulinotropic peptide is a bit of a mouthful, which is why you’ll have heard it referred to as GIP. Much simpler, right? GIP is a hormone produced in your body after you eat, and it helps insulin enter your bloodstream so it can keep your blood sugar levels in check. There are a few hormones that have similar responsibilities in your body, and this group of hormones is called incretins. Another, more widely known example of an incretin is GLP-1, which also interacts with your hunger hormones.

‘The Swiss Army knife of metabolism’: studying the uses of gut hormones around the body

Recent studies at the University of Toronto’s Termerty Faculty of Medicine have shown how gut hormones that help control insulin and blood glucose levels could also prove helpful in other areas of the body. These hormones, known as glucagon-like peptides (GLP-1 and GLP-2), were discovered some years ago by a group of researchers that included Professor Daniel Drucker, who has led the most recent studies. GLP-1 and GLP-2 are naturally occurring hormones within the body that stimulate the production of insulin, regulate blood glucose, and appear to aid weight loss by slowing digestion. In people with type 2 diabetes, these hormones are often produced at much lower levels, and are administered through medication known as GLP-1 agonists, that mimic the work of the hormone.

Resources

Glucagon.com

GIP, also known as gastric inhibitory polypeptide, or glucose-dependent insulinotropic polypeptide, is a 42 amino acid peptide hormone synthesized in and secreted from K cells in the intestinal epithelium. The majority of intestinal K cells are located in the proximal duodenum. GIP secretion is primarily regulated by nutrients, especially fats Intriguingly, bioactive truncated GIP has also been detected in pancreatic a-cells, raising the possibility of an intra-islet a-cell to b-cell connection...

StatPearls

The glucose-dependent insulinotropic polypeptide, formerly known as gastric inhibitory peptide (GIP), was first isolated in 1973 from porcine small intestine based on its ability to inhibit gastric hydrochloric acid secretion. Soon after, in 1980, GIP was found to be a weak inhibitor of acid secretion and a potent stimulator of insulin post meals.

You and Your Hormones

Glucose-dependent insulinotropic peptide is a hormone produced by the small intestine in response to eating food. Its main action is to encourage the release of insulin into the bloodstream to control blood sugar levels.