Endocrine Abstracts

Type I diabetes mellitus (DM) is characterized by an autoimmune destruction of the pancreatic β-cells that leads to absolute insulin deficiency. However, T1DM individuals undergoing exogenous insulin therapy may show partial remission of endogenous insulin secretion and better insulin sensitivity, and this remission may range between few months to many years. This partial remission is known as the ‘honeymoon phase,’ and extending the duration of this remission has been a centre stage for medical intervention towards T1DM. Since proliferation renders pancreatic β-cells immature, we aimed to investigate whether arresting cells can possibly enhance GSIS. In other words, we wanted to check whether cell cycle synchronization can possibly be an underlying reason behind the honeymoon phase. Among various cell culture model systems used for studying glucose stimulated insulin secretion (GSIS), Mouse Insulinoma 6 (Min6) cells is a widely used mouse pancreatic β-cell line which mimics pancreatic β-cell physiology. We treated Min6 cells with nocodazole (60 ng/ml) for 16 hours to arrest them at mitotic phase. An enhanced GSIS was observed at incremental EGC’s, ranging from basal (2.8 mM) to hyperglycemic (25 mM) level. The amount of secreted insulin was measured by sandwich ELISA method. The synchronization of cells was confirmed by flow cytometry. The fold change in GSIS observed for the synchronized cells was significantly higher (statistically) as compared to the non-synchronized cells. Cellular protein content as well as secreted protein content in the supernatant medium remained constant, irrespective of EGC and synchronization, as measured by Bradford method. Thus, we show that synchronization of cells or proliferative arrest can enhance GSIS and might be one of the underlying reasons behind the remission of endogenous insulin secretion in T1DM individuals, commonly known as the honeymoon phase. We propose a model at the cellular level, in which initial destruction of some β-cells results in production of new β-cells that are synchronized, thereby providing higher levels of insulin secretion from lower number of cells. Subsequently, the higher metabolic load (resulting from higher insulin secretion as shown by us earlier) experienced by lesser number of β-cells results in further cell death eventually leading to complete destruction of β-cells. To our knowledge, this is the first cellular level model that correlates well with the clinical observation of honeymoon phase in T1DM.