Pancreatic β-cell failure,clinical implications,and therapeutic strategies in type 2 diabetes

Pancreaticβ-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes(T2D).Reserving insulin-producingβ-cells and hence restoring insulin production are gaining attention in translational diabetes research,andβ-cell replenishment has been the main focus for diabetes treatment.Significant findings inβ-cell proliferation,transdifferentiation,pluripotent stem cell differentiation,and associated small molecules have served as promising strategies to regenerateβ-cells.In this review,we summarize current knowledge on the mechanisms implicated inβ-cell dynamic processes under physiological and diabetic conditions,in which genetic factors,age-related alterations,metabolic stresses,and compromised identity are critical factors contributing toβ-cell failure in T2D.The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promotingβ-cell proliferation,inducing non-β-cell transdifferentiation,and reprograming stem cell differentiation.Although a significant challenge remains for each of these strategies,the recognition of the mechanisms responsible forβ-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenousβ-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

Exercise precision medicine for type 2 diabetes:Targeted benefit or risk?

Concurrent exercise and metformin administration may reduce the acute and chronic effects of exercise on glucose metabolism in the patients with type 2 diabetes(T2D).However,several studies suggest that combing metformin and exercise treatment may have neither additive effect nor even cause adverse effects in T2D patients.This case report aimed to highlight the challenges associated with prescribing exercise to type 2 diabetes patients undergoing metformin treatment.A 67-years old woman was followed-up for five months,including assessment of the acute and chronic glucose and lactate metabolism induced by concomitant exercise and metformin.The findings were four-fold:1)During a high-intensity interval training bout,blood glucose systematically decreased,while blood lactate concentrations fluctuated randomly;2)Basal blood lactate levels were well above 2 mmol/L on days with medication only;3)Combined exercise and metformin administration induced additive effects on the normalization of glucose and 4)high levels of physical activity had a positive impact on the continuous glucose fluctuations,while decreased levels of physical activity induced a large fluctuation of glucose due to home confinement of an infectious disease caused by the SARS-CoV-2 virus.Our findings showed that when combined with exercise and metformin treatment for T2D patients,exercise may contribute to improving glycemic control while metformin may elevate lactate levels in the long term.The observed results underline the need to prescribe exercise and monitor lactate levels for reducing possible risks associated with metformin treatment and reinforce the importance of tailoring exercise therapy.