CNR1 and hyperinsulinism: In addition, in consistent with previous report in the diet-induced obese pre-diabetic mice (30), LH-21 also showed an overall metabolic improvement in glucose metabolism relevant parameters in the KKAy mice including ameliorated glucose intolerance and hyperinsulinemia, increased insulin sensitivity index, and a tendency to decrease fasting glucose; however, this may be realized through both the CB1R- and GPR55-mediated actions, as LH-21 was recently proved to be able to improve islet β-cell function and viability through directly activation of islet GPR55 (36).