OVERVIEW

Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone made up of 30-31 amino acids. Its primary role in the body is to regulate blood sugar levels by stimulating insulin secretion. Additionally, it helps preserve insulin stores by promoting insulin gene expression and has been linked to neuroprotective effects within the brain and central nervous system.

In the digestive system, GLP-1 slows gastric emptying and decreases intestinal movement, contributing to reduced appetite. Early research suggests its influence extends to various organs, including the heart, liver, muscles, bones, lungs, and kidneys.

The main focus of GLP-1 studies has been on diabetes management and appetite control, with secondary research investigating its cardiovascular benefits. More recently, growing interest has emerged regarding its potential role in preventing neurodegenerative conditions. Studies indicate that GLP-1 may slow or inhibit the buildup of amyloid beta plaques, a hallmark of Alzheimer’s disease, making it a promising area of research in cognitive health.

RESEARCH

GLP-1 and the Incretin Effect

One of GLP-1’s most significant effects is known as the “incretin effect,” a mechanism described by Dr. Holst. Incretins are metabolic hormones produced in the digestive tract that lower blood sugar levels. GLP-1, along with glucose-dependent insulinotropic polypeptide (GIP), is one of the two key incretins involved in this process. Although GIP circulates at higher levels than GLP-1, studies suggest that GLP-1 is more effective, particularly when blood sugar levels are elevated.

GLP-1 receptors are present on pancreatic beta cells, directly influencing insulin release. When used alongside sulfonylurea medications, GLP-1 can enhance insulin secretion, sometimes leading to mild hypoglycemia in a significant percentage of subjects. Insulin release not only aids blood sugar regulation but also supports protein synthesis, reduces protein breakdown, and increases amino acid absorption in skeletal muscles.

Beta Cell Support and Protection

Animal studies indicate that GLP-1 promotes the growth and regeneration of pancreatic beta cells, potentially aiding in diabetes management. It has also been observed to protect beta cells from programmed cell death (apoptosis) and may encourage the development of new beta cells from progenitor cells in the pancreas.

One notable study demonstrated that GLP-1 helps safeguard beta cells from inflammation-induced damage. In mouse models of type 1 diabetes, GLP-1 has been shown to protect islet cells from destruction, suggesting it may be useful in delaying or preventing the onset of the disease.

GLP-1 and Appetite Regulation

Research in animal models suggests that GLP-1, when administered in the brain, can suppress hunger and reduce overall food intake. It appears to enhance feelings of fullness, contributing to natural appetite control.

Clinical studies in mice have demonstrated that consistent use of GLP-1 receptor agonists leads to progressive weight loss. Over time, this weight reduction has been associated with improvements in cardiovascular health and lower hemoglobin A1C levels, an indicator of long-term blood sugar control.

Cardiovascular Benefits of GLP-1

GLP-1 receptors are found in the heart, where they help regulate cardiac function. Research suggests that GLP-1 can increase heart rate and reduce left ventricular end-diastolic pressure, which is significant since elevated pressure in this area is linked to heart failure and adverse cardiac remodeling.

Emerging studies indicate that GLP-1 may help reduce heart attack-related damage by enhancing glucose uptake in heart muscle cells. This process appears to be independent of insulin and can provide vital energy to struggling heart tissues, potentially reducing cell death.

Large-scale GLP-1 infusions in canine studies have improved heart function and decreased vascular resistance, which can help lower blood pressure and reduce long-term cardiovascular strain. Dr. Holst has noted that GLP-1 consistently enhances heart performance in both experimental models and human patients following cardiac events.

GLP-1 and Brain Health

There is growing evidence that GLP-1 may support cognitive function and protect against neurodegenerative conditions such as Alzheimer’s disease. Studies in mice have shown that GLP-1 can enhance learning and memory, even in subjects with genetic predispositions to cognitive impairment. Furthermore, animals engineered to overexpress GLP-1 receptors in specific brain regions have demonstrated superior cognitive performance compared to controls.

Additional research suggests that GLP-1 may help shield neurons from damage caused by excessive excitatory signaling. In experimental models, it has protected brain cells from glutamate-induced apoptosis and promoted nerve growth. These findings have led researchers to explore GLP-1’s potential role in slowing or even reversing neurodegenerative conditions.

Notably, studies in mice have shown that GLP-1 and its analogue, exendin-4, can reduce levels of amyloid beta, a protein associated with Alzheimer’s disease. While scientists continue to investigate whether preventing amyloid beta accumulation can alter disease progression, these findings offer promising insights into possible interventions for cognitive decline.

STRUCTURE

• Chemical Formula: C₁₈₇H₂₉₁N₄₅O₅₉
• Molecular Mass: 4113.58 g/mol
• Amino Acid Sequence: HXEGTFTSDVSSYLEGQAAK-OH.steric diacid-EFIAWLVRGRG
• CAS Registry Number: 910463-68-2
• PubChem Identifier: 56843331

CITATIONS

1. Physiology of Glucagon-like Peptide 1 | Physiological Reviews
2. Combination Therapy: Lisofylline and Exendin-4 in Autoimmune Diabetes – PubMed
3. Cardiac Protection and GLP-1: Impact on Ischemia/Reperfusion Injury | Diabetes Journal
4. GLP-1 as a Potential Alzheimer’s Disease Therapy – PubMed
5. Holst JJ. From the Incretin Concept to GLP-1-Based Diabetes Treatments. Front Endocrinol (Lausanne).