GLP-1R: A Promising Therapeutic Target in Diabetes Research

Diabetes, a chronic metabolic disorder that results from inadequate insulin secretion by the pancreas or insulin resistance in the body, has reached alarming levels worldwide. In 2021, it was estimated that over 537 million adults between 20-79 years of age would suffer from diabetes, making it one of the major threats to human life and well-being.

With the advancement in molecular target research, the development of small molecule drugs has emerged as a powerful tool for targeted therapies, gaining momentum among drug developers. In recent years, the glucagon-like peptide-1 receptor (GLP-1R) has gained considerable attention as a hot target in diabetes research.

An Overview of GLP-1R

GLP-1R, a member of the glucagon receptor subfamily within the G protein-coupled receptor cluster B, is widely expressed across various tissues, including the pancreas, brain, small intestine, heart, and lungs[2]. GLP-1 or its analogs act as natural or synthetic agonists to activate physiological functions in the body, such as stimulating insulin secretion and inhibiting glucagon secretion, thereby promoting glucose metabolism. Simultaneously, they also play a crucial role in reducing appetite and slowing down gastric emptying[3,4]. Consequently, there has been a steady increase in the development of hypoglycemic and weight-loss drugs targeting GLP-1R.

Current Market Landscape of Antidiabetic Drugs Targeting GLP-1R

Several antidiabetic drugs that act on GLP-1R have received US FDA approval and are actively marketed. With the exception of insulin, these drugs have the largest market share in the global hypoglycemic drug market, and their dominance is gradually increasing.

Table 1: Hypoglycemic drugs targeting GLP-1R with FDA approval

 (source: PHARMCUBE)

GLP-1R agonists are currently at the forefront of the global hypoglycemic drug market. As our understanding of the pathological mechanisms of GLP-1 in various diseases improves, GLP-1R agonists will likely expand their indications to encompass a wider range of disease areas, such as kidney disease, cardiovascular diseases, NASH, and others.

GLP-1R Humanized Mouse Model Developed by GemPharmatech

GemPharmatech has been actively engaged in the development of clinically relevant animal models for years and has successfully created a humanized GLP-1R mouse model (B6-hGLP-1R │ NO. T053832). This model provides a powerful tool for conducting research related to obesity drug screening and efficacy evaluation.

Validation Data for B6-hGLP-1R Mice:

Fig 2: Detection of mRNA expression in B6-hGLP-1R mice

The results showed that the human GLP-1R mRNA was highly expressed in the duodenal and lung tissues of B6-hGLP-1R mice, while murine GLP-1R mRNA was not detected.

Fig 3: Detection of protein expression in B6-hGLP-1R mice

The results showed that the human GLP-1R protein was highly expressed in the lung and pancreas of B6-hGLP-1R mice.

Drug efficacy evaluation using B6-hGLP-1R mice:

Fig 4: Blood glucose detection experiment (data from 3rd party collaboration)

Fig 5: IPGTT (data from 3rd party collaboration)

In comparison to B6-hGLP-1R mice that were fed with a Chow diet (CD), those that were fed with a high-fat diet (HFD) had higher blood sugar levels and exhibited impaired glucose metabolism as shown by fasting blood glucose (Fig 4) and glucose tolerance (Fig 5). During efficacy evaluation, both positive drugs (Sema and Tirzepatide) and the test product A demonstrated a significant hypoglycemic effect in the B6-hGLP-1R mice, affirming its potential as a suitable model for diabetes drug screening.

References:

  1. International Diabetes Federation (IDF). Global Diabetes Atlas (10th Edition). 2021
  2. Mohd MA, Koole C, et al. Molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by GLP-1R activation. British Journal of Pharmacology, 2014, 171 : 1114–1128. DOI: 10.1111/bph.12313
  3. Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors & Channels, 2011, 8 : 179–188.
  4. Francisco Kerr Saraiva , Andrei C Sposito. Cardiovascular effects of Glucagon-like peptide 1 (GLP-1) receptor agonists, 2014.10. DOI: 10.1186/s12933-014-0142-7

Most Popular

More from Author

How Do Experts Handle Post-Construction Cleaning in Charlotte with a Structured Process

What happens after a construction project is completed? Dust, debris, and...

Hornsby’s Chiropractic Experts: Proven Relief for Spinal Disc Injuries

Spinal disc injuries can cause severe discomfort, limiting mobility and affecting...

Elevate Your Health Journey with Quest 4 Health TRT

In the pursuit of optimal well-being, many individuals struggle with low...

Read Now

How Do Experts Handle Post-Construction Cleaning in Charlotte with a Structured Process

What happens after a construction project is completed? Dust, debris, and leftover materials must be removed before the place is ready for use. A structured cleaning process ensures everything is spotless. Let’s explore how experts handle post-construction cleaning in Charlotte. Removing Large Debris and Construction Waste The first step...

Hornsby’s Chiropractic Experts: Proven Relief for Spinal Disc Injuries

Spinal disc injuries can cause severe discomfort, limiting mobility and affecting daily life. These injuries occur when the discs between the vertebrae are damaged, leading to pain, inflammation, and nerve compression. Whether caused by aging, poor posture, or an accident, spinal disc injuries require specialized care. Seeking...

Extended Stay Near Hospitals: The Essential Guide for Families and Caregivers

When a loved one is admitted to a hospital for an extended period, family members often face the challenge of finding a place to stay nearby. For those who need to be close to the hospital for regular visits or to provide ongoing support, an extended stay...

Elevate Your Health Journey with Quest 4 Health TRT

In the pursuit of optimal well-being, many individuals struggle with low energy, weight gain, mood swings, and declining vitality—especially as they age. While diet and exercise are crucial, hormonal imbalances can often be the hidden obstacle preventing you from reaching your peak health.  Quest 4 Health TRT (Testosterone...

Building Trust and Communication Through Couple Counseling

The foundation of a strong relationship depends on good communication and trust between partners. The basic structure of trust and good communication lets partners understand each other better but their absence causes emotional separation. Couple therapy creates an organized system to help partners reestablish their trust and...

How PRP and Stem Cells Are Transforming Aesthetic Procedures

The field of aesthetic medicine has evolved dramatically in recent years, with regenerative medicine emerging as one of the most transformative advancements. By harnessing the body’s natural healing processes, regenerative medicine aims to repair, restore, and rejuvenate tissues in a way that traditional cosmetic treatments cannot. Platelet-rich...