(#48) Cellular distribution of Golli protein in human pancreatic islets

PRESENTED BY: Ji-Ming Feng

Authors
First NameLast NameAffiliation/Institution
Ji-MingFengLouisiana State University
 

Purpose

This project is to determine the cellular distribution of Golli protein in human pancreatic islets. Golli (gene expressed in oligodendrocyte lineage) is an alternatively spliced product of myelin basic protein (MBP) gene featured by the presence of a unique Golli domain which contains a 133-amino-acid sequence fused in the N-terminal of classic MBP. The Golli peptide shares 79% homology between the human and the mouse. Our works in mouse have identified that Golli protein serves as an important regulator of Ca2+ release –activated Ca2+ (CRAC) channel in T lymphocytes and voltage-dependent calcium channel (VDCC) in oligodendrocytes and neurons. This proposal start from our original findings in mice that: Golli protein is expressed in β cells of mouse Langerhans islet and plays a critical role in insulin secretion. We propose here to investigate the cellular distribution of Golli protein in human pancreas (both normal and type-1 and -2 diabetic) tissues, and we aim to build up a direct correlation of our findings of Golli in rodents to type-1 and type-2 diabetes in human.
 

Methods

Paraffin sections of human pancreatic tissue from nPOD were stained by immunohistochemistry with Golli antibody (specific to human Golli peptide) in conjunction with other islet cell markers (insulin, glucagon, IAPP).
 

Summary of Results

With the generous support by the Helmsley Charitable Trust George S. Eisenbarth nPOD Award for Team Science, we have finished a pilot experiment of Golli immunostaining in pancreas tissue from 5 nondiabetic controls (#6015, 6017, 6030, 6034 and 6254), 5 T1D patients (#5000, 6035, 6045, 6046 and 6299), and 1 T2D patient (#6249) with amyloid. Interestingly, we have found that 1) Golli immunostaining is found in all type of islet endocrine cells from nondiabetic human pancreas; 2) Dramatic (greatly) reduced Golli immunostaining in Ins+/GCG+ islets of T1D patients (#5000 and #6046, these two patients still have insulin positive islets, as early-staged T1D), reduced level of Golli immunostaining in all islet endocrine cells, especially evident in β cells; 3) In late-staged T1D patients whose islets contain only α cells, Golli immunostaining reduced slightly (some islets in #6035) or no change (#6045 and 6299); 4) Moderate Golli immunostaining is found in islet amyloid plaque of T2D patient (#6249).
 

Conclusions

Golli protein is specifically expressed in islet endocrine cells (both alpha and beta cells) in healthy human islets. Their expression level in beta cells is dramatically reduced in early staged type-1 diabetic patients when impaired insulin secretion occurs, suggesting a role of Golli protein in regulation of insulin secretion during type-1 diabetes. The presence of Golli immunostaining in amyloid of T2D islets may indicate a role of Golli protein in islet amyloidosis during typ-2 diabetes.