Sympathetic Innervation of Pancreatic Islets in Individuals with Type 1 Diabetes (T1D)
The pancreatic islet, a cluster of highly-innervated and vascularized hormone-producing endocrine cells, secretes insulin and glucagon to regulate the blood glucose. T1D results from the autoimmune destruction of the insulin-producing beta cells leading to insulin deficiency and requiring insulin injections. Individuals with T1D receiving insulin therapy are at risk of low blood glucose, due to an impaired glucagon-secretory response by the alpha cell, which can be life-threatening. Glucagon secretion is regulated by the sympathetic nervous system and by metabolic stimuli impacting the alpha cell. It is unknown whether the mechanism behind the impaired glucagon-secretory response in T1D is due to defects in islet innervation or intrinsic alterations in the alpha cell.
To test the hypothesis that the sympathetic innervation of the pancreatic islet is altered in T1D, we have studied pancreatic tissue from individuals with recent-onset T1D (n=4; ages 12-20yrs, duration 3-10yrs) and longstanding T1D (n= 4; ages 27-63yrs, duration 17-44yrs) in comparison to age-matched controls (n=5; ages 10-55yrs). To quantify the sympathetic innervation in the pancreatic islets, we are performing immunohistochemistry on pancreatic cryosections for glucagon+ alpha cells and tyrosine hydroxylase (TH)+ sympathetic nerve fibers. While our studies are ongoing, we hypothesize that longer duration of T1D leads to decreased sympathetic innervation of the pancreatic islet and predict a decreased density of islet-associated TH+ nerve fibers in the long-standing T1D pancreas. Understanding the mechanisms behind the impaired glucagon-secretory response to hypoglycemia in T1Ds should direct future efforts to reverse this complication of T1D.