Function of pramlintide in diabetes
Pramlintide is a synthetic analogue of pancreatic amyloid polypeptide. Pancreatic amyloid polypeptide is a polypeptide hormone composed of 37 amino acid residues, which has a stable regulation of human blood sugar. The difference between the amino acid sequence of the pramlintide and the pancreatic amyloid polypeptide showed that the former 25 (alanine), 28 (serine) and 29 (serine) were replaced by proline. Studies have shown that pramlintide can reduce the frequency and amplitude of blood glucose fluctuation in diabetic patients and improve the overall glycemic control.
Figure 1 The arrangement of 37 amino acids in the pramlintide. (Yuan et al. 2018)
The main hypoglycemic mechanism of pramlintide is to inhibit the release of glucagon, delay gastric emptying and inhibit food intake. Under physiological condition, postprandial blood glucose rises, insulin secretion increases, glucagon secretion decreases, blood sugar is maintained within normal limits. In diabetics with insulin deficiency, this feedback mechanism is damaged, and it is found that insulin injection alone cannot achieve good hypoglycemic effect in patients with diabetes. The addition of pramlintide after insulin injection can significantly reduce the blood sugar of diabetics.
Pramlintide can be used as an adjuvant therapy for type 1 and type 2 diabetes, mainly for insulin alone, and in diabetic patients who are still in combination with insulin and sulfonylureas and/ormetformin. Pramlintide can be used with insulin, but it cannot replace insulin. Furthermore, it has a variety of physiological functions, such as slowing down the absorption of food (including glucose) in the small intestine, reducing the production of glycogen by inhibiting hyperglycemic, reducing the appetite of the patients, and assisting the body to regulate blood sugar.
Pharmacokinetics and metabolism
Pancreatic amyloid polypeptide is a polypeptide hormone made up of 37 amino acid residues. It is released by pancreatic beta cells after meal. It has been proved that pramlintide can delay the absorption of glucose, inhibit the secretion of glucagon and reduce the formation and release of liver sugar, thus it can reduce the frequency and amplitude of blood glucose fluctuation and improve the overall blood glucose control in diabetic patients. The absolute bioavailability of pramlintide peptide is 30% to 40%, the peak time is about 20 minutes, and the half-life is about 50 minutes. pramlintide is mainly metabolized and excreted by the kidney. The half-life of its metabolite Des-lyspramlintide is similar to that of pramlintide.
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