The Incretin Effect of Semaglutide

Perhaps the most important effect that Semaglutide has, according to Dr. Holst, is referred to as the “incretin effect.” Incretins are a group of metabolic hormones, released by the GI tract, that cause a decrease in blood glucose (sugar) levels. Semaglutide has been shown to be one of the two most important hormones (the other being GIP) to stimulate the incretin effect in rodent models. Though GIP circulates at levels roughly 10 times higher than that of Semaglutide, there is evidence that Semaglutide is the more potent of the two molecules, particularly when levels of blood glucose are quite high.

A Semaglutide receptor has been identified on the surface of pancreatic beta cells, making it clear that Semaglutide directly stimulates the exocytosis of insulin from the pancreas. When combined with sulfonylurea drugs, Semaglutide has been shown to boost insulin secretion enough to cause mild hypoglycemia in up to 40% of subjects. Of course, increased insulin secretion is associated with a number of trophic effects including increased protein synthesis, reduction in the breakdown of protein, and increased uptake of amino acids by skeletal muscle.

Semaglutide and Beta Cell Protection

Research in animal models suggests that Semaglutide can stimulate the growth and proliferation of pancreatic beta cells and that it may stimulate the differentiation of new beta cells from progenitors in the pancreatic duct epithelium. Research has also shown that Semaglutide inhibits beta cell apoptosis. Taken in sum, these effects tip the usual balance of beta cell growth and death toward growth, suggesting that the peptide may be useful in treating diabetes and in protecting the pancreas against insult that harms beta cells.

In one particularly compelling trial, Semaglutide was shown to inhibit the death of beta cells caused by enhanced levels of inflammatory cytokines. In fact, mouse models of type 1 diabetes have revealed that Semaglutide protects islet cells from destruction and may, in fact, be a useful means of preventing the onset of type 1 diabetes.

Semaglutide and Appetite

Research in mouse models suggests that administration of Semaglutide, and its similar cousin GLP-1, into the brains of mice can reduce the drive to eat and inhibit food intake. It appears that Semaglutide may actually enhance feelings of satiety, helping individuals to feel fuller and reducing hunger indirectly. Recent clinical studies have shown in mice that twice-daily administration of Semaglutide receptor agonists causes gradual, linear weight loss. Over a long period, this weight loss is associated with significant improvement in cardiovascular risk factors and a reduction in hemoglobin A1C levels, the latter of these being a proxy marker for the severity of diabetes and the quality of blood sugar control attained via treatment.

Potential Cardiovascular Benefits of Semaglutide

It is now known that Semaglutide receptors are distributed throughout the heart and act to improve cardiac function in certain settings by boosting heart rate and reducing left ventricular end-diastolic pressure. The latter may not seem like much, but increased LV end-diastolic pressure is associated with LV hypertrophy, cardiac remodeling, and eventual heart failure.

Recent evidence has even suggested that Semaglutide could play a role in decreasing the overall damage caused by a heart attack. It appears that the peptide improves cardiac muscle glucose uptake, thereby helping struggling ischemic heart muscle cells to get the nutrition they need to continue functioning and avoid programmed cell death. The increase in glucose uptake in these cells appears to be independent of insulin.

Large infusions of Semaglutide into dogs have been shown to improve LV performance and reduce systemic vascular resistance. The latter effect can help to reduce blood pressure and ease strain on the heart as a result. This, in turn, can help to reduce the long-term consequences of high blood pressure such as LV remodeling, vascular thickening, and heart failure. According to Dr. Holst, administration of Semaglutide following cardiac injury has “constantly increased myocardial performance both in experimental animal models and in patients.”

Semaglutide and the Brain

There is some evidence to suggest that Semaglutide can improve learning and help to protect neurons against neurodegenerative diseases such as Alzheimer’s disease. In one study, Semaglutide was shown to enhance associative and spatial learning in mice and even to improve learning deficits in mice with specific gene defects. In rats that over-express the Semaglutide receptor in certain regions of the brain, learning and memory are both significantly better than in their normal controls.

Additional research in mice has shown that Semaglutide can help to protect against excitotoxic neuron damage, completely protecting rat models of neurodegeneration against glutamate-induced apoptosis. The peptide can even stimulate neurite outgrowth in cultured cells. Researchers are hopeful that additional research on Semaglutide will reveal how it might be used to halt or reverse certain neurodegenerative diseases.

Interestingly, Semaglutide and its analogue exendin-4 have been shown in mouse models to reduce levels of amyloid-beta in the brain as well as the beta-amyloid precursor protein found in neurons. Amyloid beta is the primary component of the plaques observed in Alzheimer’s disease, plaques which, while not necessarily known to be causative, are associated with the severity of the disease. It remains to be seen if preventing amyloid beta accumulation can protect against the effects of Alzheimer’s disease, but this research is, at the very least, a tantalizing clue as to how scientists might intervene in the progression of mild cognitive impairment to full Alzheimer’s disease.

Semaglutide exhibits minimal to moderate side effects, low oral, and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. Semaglutide for sale at Peptide Sciences is limited to educational and scientific research only, not for human consumption. Only buy Semaglutide if you are a licensed researcher.