A minimal mathematical model to study insulin synthesis and secretion process

Abstract

Insulin, secreted from pancreatic β-cells, plays a vital role in maintaining glucose homeostasis in our body. In various pathophysiological conditions like diabetes, cancer, etc., this glucose-insulin relationship is altered. However, the underlying mechanisms behind the β-cell malfunctioning under these pathophysiological conditions remain a research topic. The current study aimed to explore the key factors responsible for impaired insulin secretion from β-cells. We studied insulin synthesis and secretion processes through a minimal mathematical model incorporating insulin mRNA, proinsulin pool, and insulin granules. Defects in the insulin granule trafficking and exocytosis processes hamper first- and second-phase insulin secretion and might be one of the main reasons for β-cell dysfunction in type 2 diabetes. The long-term effect of abnormal insulin synthesis could hamper insulin secretion and make the scenario more critical, causing complete insulin loss inside the β-cells. Besides, uncontrolled insulin synthesis could increase basal insulin secretion and drive toward fasting hypoglycemia. The present study also hypothesizes that regulation of insulin synthesis through targeting transcription and translation is a potential therapeutic strategy for controlling impaired insulin secretion.