Paracrine factors regulate glucagon trafficking through the Stmn2-mediated lysosomal network
Abstract
In diabetes, excess glucagon secretion and insulin deficiency contribute to disease progression and hyperglycemia. Understanding the intracellular trafficking of glucagon in alpha cells can reveal potential therapeutic targets to alleviate hyperglycemia. Stathmin-2 (Stmn2) was previously found in the secretory granules of αTC1-6 cells and was hypothesized to direct glucagon to lysosomes for degradation. My work aims to investigate whether paracrine inhibition of glucagon secretion operates through the Stmn2-mediated lysosomal pathway.
I manipulated Stmn2 levels and applied paracrine treatment to observe glucagon and lysosome distribution using microscopy. I found that Stmn2 was essential in mediating paracrine redistribution of glucagon and lysosomes. Microscopy also showed strong colocalization and similar distribution of Stmn2 and lysosomes in both mouse and human alpha cells, while qPCR analysis showed that Stmn2 upregulated autophagy genes.
In summary, my thesis describes a potential regulator of glucagon secretion with therapeutic potential for hyperglucagonemia and hyperglycemia of diabetes.