Mark D. Erion

TL;DR: Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond, suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.

TL;DR: MK-8722 is developed, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes that induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia in rodents and rhesus monkeys.

TL;DR: It is concluded that GCGR agonism concomitant with GLP1R agonism constitutes a promising approach to treatment of the metabolic syndrome, however, the relative ratio of GLP 1R/GCGR co‐agonism needs to be carefully chosen for each species to maximize weight loss efficacy and minimize hyperglycemia.

TL;DR: Clinical evaluations of CS-917 revealed a favorable safety profile as well as clinically meaningful reductions in fasting glucose levels in patients with T2DM, and future trials of MB07803, a second generation FBPase inhibitor with improved pharmacokinetics, will address whether this novel class of antidiabetic agents can provide safe and long-term glycemic control.

TL;DR: Results provide a novel finding by which glucagon and, hence, GCGR antagonism govern cholesterol metabolism, and link MK-0893 with increased glucagon-like peptide 2 and cholesterol absorption.