In recent years

tremendous progress has been made on beta cell dysfunction and insulin resistance

2 fundamental pathological mechanisms of type 2 diabetes mellitus (T2DM).  Reduced beta-cell mass has been widely accepted as the main cause leading to insulin secretion decline

the machanism of which has been attributed to enhanced beta-cell apoptosis

beta-cell dedifferentiation

and decreased beta-cell proliferation. Also having made a great breakthrough is the study on insulin resistance

particularly in obesity condition. Chronic systemic inflammation has now been recognized as the link between obesity

insulin resistance and T2DM. The enlarged adipose tissue is now recognized as the major source for the enhanced release of various bioactive adipokines and proinflammatory factors

such as leptin

resistin and TNF-α

which act as mediators for impaired insulin signaling in the liver

muscles and central nervous system. Supported in evidence

weight-loss by bariatric surgery has achieved great success in reducing the metabolic risk factors for T2DM and is the most effective treatment for morbid obese patients. These studies and clinical practice underscore adipose tissue and the gastrointestinal tract as important endocrine organs in maintenance of glucose homeostasis. Besides

the role of gut microbiota  in the development of insulin resistance and metabolic disorders has been established. This review highlighted these recent progresses in mechanisms of T2DM with emphasis on the loss of beta cell mass and obesity-associated insulin resistance.