Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Mitophagy is essential for cellular homeostasis but the regulatory mechanism is largely unknown. Here we report that the kinase Jnk2 is required for stress-induced mitophagy. Jnk2 promoted ubiquitination and proteasomal degradation of small mitochondrial form of ARF (smARF). Loss of Jnk2 led to accumulation of smARF, which in turn induced excessive autophagic activity, resulting in lysosomal degradation of the mitophagy adaptor p62 in the steady state. The depletion of p62 prevented Jnk2-deficient cells from mounting mitophagy upon stress. Jnk2-deficient mice displayed defective mitophagy, resulting in tissue damage under hypoxic stress, as well as hyperactivation of inflammasome and increased mortality in sepsis. Our finding defines a unique mechanism of maintaining immune homeostasis that protects the host from tissue damage and mortality.

A wide range of microalbuminuria cutoff values are currently used for diagnosing the early stage of nephropathy in type 2 diabetes (T2D). This study analyzed the relationships between oxidant and antioxidant markers of nephropathy and the severity of microalbuminuria. The study included 50 healthy controls (Group 1), 50 diabetic patients with no nephropathy (Group 2), 50 diabetic patients with nephropathy and a urinary albumin excretion (UAE) of 30–200 mg/24 h (Group 3), and 50 diabetic patients with UAE 200–300 mg/24 h (Group 4). Serum nitrotyrosine, conjugated dienes, 8-hydroxy-2′-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) levels were determined. Oxidative stress is increased in the early stage of nephropathy in patients with T2D. There was a significant correlation between the extent of microalbuminuria and markers of oxidative stress. Multiple linear regression analysis identified lipid oxidative stress as a possible independent marker for evaluating the degree of renal damage in diabetic nephropathy. Stratifying microalbuminuria values during the early stage of nephropathy might be an important factor in facilitating earlier and more specific interventions.

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