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Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition, incretin receptor expression in β-cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Clinically, it is important to select appropriate therapy for type 2 diabetes mellitus (T2DM) so that β-cell function can be preserved. In addition, when appropriate pharmacological interventions against β-cell glucose toxicity are started at the early stages of diabetes, β-cell function is substantially restored, which is not observed if treatment is started at advanced stages. These observations indicate that it is likely that downregulation of pancreatic transcription factors and/or incretin receptors is involved in β-cell dysfunction observed in T2DM and it is very important to start appropriate pharmacological intervention against β-cell glucose toxicity in the early stages of diabetes., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

It is known that reactive oxygen species (ROS) are involved in the development of insulin resistance as well as pancreatic β-cell dysfunction both of which are often observed in type 2 diabetes. In this study, we evaluated the effects of azelnidipine, a calcium channel blocker, on ROS-mediated insulin resistance in adipocytes. When 3T3-L1 adipocytes were exposed to ROS, insulin-mediated glucose uptake was suppressed, but such phenomena were not observed in the presence of azelnidipine. Phosphorylation of insulin receptor and phosphorylation of Akt were suppressed by ROS, which was mitigated by azelnidipine treatment. Activation of the JNK pathway induced by ROS was also reduced by azelnidipine. Various inflammatory cytokine levels were increased by ROS, which was also suppressed by azelnidipine treatment. In contrast, adiponectin mRNA and secreted adiponectin levels were reduced by ROS, which was refilled by azelnidipine treatment. In conclusion, azelnidipine preserves insulin signaling and glucose uptake against oxidative stress in 3T3-L1 adipocytes.

A 29-year-old woman was diagnosed as having type 1 diabetes mellitus and received insulin aspart and NPH insulin (NovolinN). On day 22, she had leg edema and right abdominal pain. The serum hepatobiliary enzyme levels were markedly elevated. Computed tomography revealed gallbladder edema. After an injection of human regular insulin and NPH insulin (HumacartN), the elevated liver enzyme levels were no longer observed. Challenge testing demonstrated that protamine was the cause of her allergy. Furthermore, tests revealed increased VEGF levels. This is an extremely rare case with a delayed-type protamine allergy caused by NovolinN resulting in gallbladder edema.

A letter to the editor is presented about the case of an 80-year-old woman with insulin autoimmune syndrome (IAS).