A glucose-responsive insulin therapy protects animals against hypoglycemia

• DOI: 10.1172/jci.insight.97476
• Publication Date: 2018-01-10T16:00:43Z
• Authors: Ruojing Yang; Margaret Wu; Songnian Lin; Ravi P. Nargund; Xinghai Li; Theresa Kelly; Lin Yan; Ge Dai; Ying Qian; Qing Dallas-yang; Paul A. Fischer; Yan Cui; Xiaolan Shen; Pei Huo; Danqing Dennis Feng; Mark D. Erion; David E. Kelley; James Mu
• Keywords: Blood Glucose; Male; 0301 basic medicine; Macrophages; Hypoglycemia; Receptor, Insulin; Cell Line; Rats; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Glucose; Mannose-Binding Lectins; Diabetes Mellitus, Type 2; Liver; Antigens, CD; Animals; Hypoglycemic Agents; Insulin; Lectins, C-Type; Mannose Receptor

Hypoglycemia is commonly associated with insulin therapy, limiting both its safety and efficacy. The concept of modifying to render glucose-responsive release from an injection depot (of complexed exogenously a recombinant lectin) was proposed approximately 4 decades ago but has been challenging achieve. Data presented here demonstrate that mannosylated analogs can undergo additional route clearance as result their interaction endogenous mannose receptor (MR), this occur in glucose-dependent fashion, increased binding MR at low glucose. Yet, these retain capacity for the (IR). When blood glucose level elevated, individuals diabetes mellitus, diminishes due competition, leading reduced MR-mediated partitioning IR consequent lowering. These studies locus and, hence, action be achieved by targeting concurrently.