XXXX in Type 2 Diabetes: A Vicious Circle?

@entity1 @entity1025 @entity6 @entity1272 @entity2690 @entity8277 @entity2412 @entity141
Over the past decades, @entity1272 (serum @entity1025 <0.7 mmol/L) has been strongly associated with @entity6 ( @entity6 ). @entity1 with @entity1272 show a more rapid disease progression and have an increased risk for @entity2412 . Clinical studies demonstrate that @entity6 @entity1 with @entity1272 have reduced pancreatic b-cell activity and are more @entity2690 resistant. Moreover, dietary @entity1025 supplementation for @entity1 with @entity6 improves glucose metabolism and @entity2690 sensitivity. Intracellular @entity1025 regulates glucokinase, KATP channels, and L-type @entity141 channels in pancreatic b-cells, preceding @entity2690 secretion. Moreover, @entity8277 autophosphorylation is dependent on intracellular @entity1025 concentrations, making @entity1025 a direct factor in the development of @entity2690 resistance. Conversely, @entity2690 is an important regulator of @entity1025 homeostasis. In the kidney, @entity2690 activates the renal @entity1025 channel transient receptor potential melastatin type 6 that determines the final urinary @entity1025 excretion. Consequently, @entity1 with @entity6 and @entity1272 enter a vicious circle in which @entity1272 causes @entity2690 resistance and @entity2690 resistance reduces serum @entity1025 concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of @entity1025 on @entity2690 secretion and @entity2690 signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to @entity1272 in @entity6 .
