PHRM 211 Lecture Notes - Lecture 7: Sglt2, Proximal Tubule, Renal Glucose Reabsorption
Document Summary
Med chem of diabetes drug (part 4) Found in proximal renal tubules (s1 & s2 segments) Responsible for reabsorbing glucose that has been filtered (90%) Inhibition reduces absorption of filtered glucose & lower renal threshold for glucose increases urinary glucose excretion. Low affinity sodium-glucose co-transporter (sglt1 is high affinity) C-glycosyl linkage between glucose & poly-aromatic chain. Glucose portion sglt2 recognition in proximal tubule. Canagliflozin 250x selectivity toward sglt2 over sglt1. Membrane-bound enzyme present on brush border cells of the small intestine (high concentration in proximal part of the jejunum) Catalyzes hydrolytic conversion of maltose & sucrose into glucose absorbed by enterocytes of jejunum to enter circulation. Prevent breakdown of complex cho into glucose (not absorbed in small intestine) Contained noted differences to natural glucan substrate ( n-glycosidic bond ) Competitive inhibitor high affinity for sucrase & less for glucoamylase and pancreatic -amylase. Acarbose does not reach systemic circulation (but miglitol. & voglibose do with no serious side effects).
