Pharmacological effect
Target: Amylin receptor (calcitonin receptor + RAMP3 complex receptor, mainly acting on AP/NTS in the posterior brainstem). Human pancreatic β cells normally secrete insulin and amylin simultaneously. In type 1 diabetes and advanced type 2 diabetes, β cells are damaged and amylin is deficient. Praline peptide as an alternative hormone has a triple effect:
1. Delay gastric emptying, slow down carbohydrate absorption, and lower the peak blood sugar level after meals; It does not affect fasting blood sugar
2. Inhibit postprandial glucagon secretion and reduce liver sugar output
3. The central nervous system increases satiety, suppresses appetite, reduces food intake, and leads to mild weight loss
Structural modification: Natural human amylin is prone to aggregation and precipitation. Replacing the amino acids at positions 25, 28 and 29 with Pro (proline) significantly enhances water solubility and stability.
Administration: Subcutaneous injection before each meal. It has a short half-life and must be used with meals. It cannot be used alone and can only be combined with insulin at meal times
IDA