Rodrigo Gatica

The pancreatic islets of Langerhans, mainly formed by glucagon‐producing α‐cells and insulin‐producing β‐cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi‐hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of α‐cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic α‐cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for α‐cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in α‐cell metabolism.

Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by pancreatic β cells, the resistance of peripheral tissues to the action of the hormone, or both, and is characterized by chronic hyperglycemia leading to organ damage and failure. Tight glycemic control represents the best therapy to delay or stop progression of diabetes, with many antidiabetic drugs being commercially available nowadays. However, no ideal normoglycemic agent has been developed as yet, and those already available still induce hypoglycemia and/or weight gain as major side effects, worsening glycemic control. In this respect, the inorganic salt sodium tungstate (Na ₂ WO ₄ ) has been proven to offer a good antidiabetic alternative in different animal models of diabetes, reducing body weight and normalizing glycemia without causing hypoglycemic episodes. The mechanisms of action mediating the potent antidiabetic actions but also the spectrum of undesirable effects of Na ₂ WO ₄ are still poorly understood. In fact, along with its beneficial effects, Na ₂ WO ₄ has been consistently reported to be toxic and even carcinogenic. Given that Na ₂ WO ₄ is accumulated in the kidneys for elimination, here, we discuss a possible association between long‐term Na ₂ WO ₄ treatment and a higher risk of renal carcinogenesis in diabetic individuals.