GLP 1 Receptor Agonists and DPP 4 Inhibitors Mechanism of Action

Summary

This video explains the mechanisms of action of GLP-1 receptor agonists and DPP-4 inhibitors, both used in the treatment of diabetes. It highlights the role of incretins, such as GLP-1, in regulating insulin release after food intake. GLP-1 receptor agonists like exenatide and liraglutide mimic GLP-1, stimulating insulin release directly, while DPP-4 inhibitors, such as sitagliptin, prevent GLP-1 degradation, enhancing its natural effects on insulin secretion. Both approaches ultimately help increase insulin release to manage blood glucose levels, making them effective therapies in diabetes management.

Takeaways

• 😀 Incretins are gut hormones released after eating food, including GLP-1 and GIP.
• 😀 GLP-1 acts on GLP-1 receptors on β cells in the pancreas to stimulate insulin release.
• 😀 GLP-1 receptors are Gs protein-coupled receptors, which activate adenylyl cyclase and increase cAMP levels.
• 😀 Dipeptidyl peptidase-4 (DPP-4) degrades GLP-1, limiting its action in the body.
• 😀 In diabetes, insulin release is impaired, so targeting GLP-1 receptors is a potential therapeutic option.
• 😀 GLP-1 itself has a very short half-life (1-2 minutes), making it impractical for use as a drug.
• 😀 GLP-1 analogues, such as exenatide and liraglutide, are resistant to DPP-4 degradation and can be used therapeutically.
• 😀 GLP-1 receptor agonists, such as exenatide and liraglutide, directly stimulate GLP-1 receptors and promote insulin release.
• 😀 DPP-4 inhibitors, like sitagliptin and saxagliptin, prevent the degradation of endogenous GLP-1, enhancing its insulin-releasing effect.
• 😀 GLP-1 receptor agonists and DPP-4 inhibitors both aim to increase insulin release, but through different mechanisms—direct stimulation versus preserving endogenous GLP-1.

Q & A

What are incretins and what role do they play in the body?

Incretins are hormones released from the gut after food intake, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). They play a crucial role in stimulating insulin release from the pancreas to manage post-meal blood glucose levels.

Why is GIP not focused on in the discussion of GLP-1 receptor agonists and DPP-4 inhibitors?

GIP has a relatively poor action in diabetes, which makes it less relevant in the context of treating diabetes compared to GLP-1, which has a more significant effect on insulin release.

What is the mechanism of action of GLP-1 in the body?

GLP-1 acts on GLP-1 receptors found on beta cells in the pancreas. It is a Gs protein-coupled receptor that activates adenylyl cyclase, converting ATP into cyclic AMP (cAMP), which in turn stimulates insulin release to regulate blood glucose levels.

Why can't native GLP-1 be used therapeutically in diabetes treatment?

Native GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4) in the body, and its plasma half-life is only 1-2 minutes, making it unsuitable for therapeutic use.

What are the two solutions to the problem of GLP-1 degradation in diabetes treatment?

The two solutions are GLP-1 analogues, which are resistant to DPP-4 degradation, and DPP-4 inhibitors, which prevent the degradation of endogenous GLP-1.

How do GLP-1 receptor agonists work to treat diabetes?

GLP-1 receptor agonists, such as exenatide and liraglutide, are analogues of GLP-1 that resist degradation by DPP-4. They directly stimulate GLP-1 receptors on beta cells, leading to increased insulin release and better blood glucose control.

What role do DPP-4 inhibitors play in diabetes treatment?

DPP-4 inhibitors, such as sitagliptin and saxagliptin, prevent the degradation of endogenous GLP-1. This increases the effect of GLP-1 on beta cells, leading to enhanced insulin release and improved blood glucose management.

What are some examples of GLP-1 receptor agonists?

Some examples of GLP-1 receptor agonists include exenatide, liraglutide, albiglutide, and dulaglutide.

What are the key differences between GLP-1 receptor agonists and DPP-4 inhibitors?

GLP-1 receptor agonists are GLP-1 analogues that directly stimulate GLP-1 receptors to release insulin, whereas DPP-4 inhibitors work by preventing the degradation of endogenous GLP-1, thereby enhancing its effect on insulin release.

What is the overall effect of both GLP-1 receptor agonists and DPP-4 inhibitors in diabetes treatment?

Both GLP-1 receptor agonists and DPP-4 inhibitors ultimately increase insulin release from beta cells in the pancreas, but they do so through different mechanisms—GLP-1 receptor agonists directly stimulate GLP-1 receptors, while DPP-4 inhibitors prevent the degradation of endogenous GLP-1.