![]() In healthy rodent islets, some PI is secreted along with CP and insulin when beta cells are stimulated. While not typically measured as a clinically useful marker of beta cell secretory function, serum PI has been reported to be elevated in relation to CP (increased PI:CP ratio) in individuals who are at increased risk for development of T1D, as well as soon after diagnosis. Proinsulin is then transported to the Golgi apparatus to become incorporated into a new “immature” beta-granule where it is subsequently cleaved into equimolar amounts of insulin and CP via prohormone convertases (PCSK1, PCSK2, and carboxypeptidase E), marking the transformation to a mature beta-granule, ready for exocytosis in response to various stimuli. Preproinsulin is synthesized in the rough endoplasmic reticulum of the beta cell and translocated to the cytosol of the rough endoplasmic reticulum where it is converted to proinsulin (PI). Normal insulin biosynthesis is a multi-step process, beginning with a pre-prohormone, preproinsulin. Measurement of serum CP concentrations during a standardized mixed meal tolerance test (MMTT) is a well-established, practical method of assessing nutrient stimulated beta cell secretory function, with peak CP concentrations > 0.2 nmol/L being associated with improved glycemic control, less hypoglycemia and fewer microvascular complications in individuals living with T1D. Recently, the long standing dogma that beta cells do not function in T1D has been challenged as endogenous insulin secretion measured by C-peptide (CP) appears to persist for decades in many individuals with long standing TID. This process precedes the diagnosis of overt hyperglycemia in most individuals, and ultimately progresses to result in near-absolute beta-cell failure, leading to life-long exogenous insulin dependence. Type 1 diabetes mellitus (T1D) is characterized by T-cell-mediated autoimmune destruction of insulin secreting pancreatic beta cells. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the manuscript and its Supporting Information files.įunding: This work was supported by Boston University Clinical and Translational Science Institute (BU-CTSI) Pilot Grant Program (NIH ID: 1UL1TR001430) and the Helmsley Charitable Trust Foundation to DWS. Received: SeptemAccepted: OctoPublished: November 9, 2018Ĭopyright: © 2018 Sullivan et al. von Herrath, La Jolla Institute for Allergy and Immunology, UNITED STATES Citation: Sullivan CA, Cacicedo JM, Rajendran I, Steenkamp DW (2018) Comparison of proinsulin and C-peptide secretion in healthy versus long-standing type 1 diabetes mellitus cohorts: A pilot study. ![]()
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