β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes

In a society where physical activity is limited and food supply is abundant, metabolic diseases are becoming a serious epidemic. Metabolic syndrome (MetS) represents a cluster of metabolically related symptoms such as obesity, hypertension, dyslipidemia, and carbohydrate intolerance, and significantly increases type 2 diabetes mellitus risk. Insulin resistance and hyperinsulinemia are consistent characteristics of MetS, but which of these features is the initiating insult is still widely debated. Regardless, both of these conditions trigger adverse responses from the pancreatic beta cell, which is responsible for producing, storing, and releasing insulin to maintain glucose homeostasis. The observation that the degree of beta cell dysfunction correlates with the severity of MetS highlights the need to better understand beta cell dysfunction in the development of MetS. This Review focuses on the current understanding from rodent and human studies of the progression of beta cell responses during the development of MetS, as well as recent findings addressing the complexity of beta cell identity and heterogeneity within the islet during disease progression. The differential responses observed in beta cells together with the heterogeneity in disease phenotypes within the patient population emphasize the need to better understand the mechanisms behind beta cell adaptation, identity, and dysfunction in MetS.