title: Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: pathophysiological hypothesis.
abstract: Primarily the sodium-glucose cotransporter 2 (SGLT2) inhibitors suppress the cotransport of glucose and sodium from the tubular lumen of proximal tubules to the blood and enhance the glucose excretion into urine. Therefore, glucose and caloric balances become negative, making the blood glucose level as well as insulin secretion both reduced. On the other hand, the proximal tubular fluid, constituting with low chloride concentration because of SGLT2 inhibition, is transferred to the loop of Henle. On the low chloride conditions, the reabsorption mechanisms in the loop of Henle do not work, as if loop diuretics are given. Finally, blood pressure is also lowered secondarily due to the loop diuretic action by SGLT2 inhibitions. Thus, the metabolic and hemodynamic combined systems synergistically interact further to suppress the risks leading to atherosclerosis and organs damage. Precise mechanisms for SGLT2 inhibitors to work in various aspects especially in preventing organ damage and cardiovascular events must be clarified further.
authors.affiliation: Asahi Rosai Hospital, Japan Labour Health and Welfare Organization, Owariasahi, Japan; Nagoya City University Medical School. Electronic address: genki@asahih.rofuku.go.jp.
authors.forename: Genjiro
authors.initials: G
authors.lastname: Kimura
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006029:Glycosuria / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008019:Life Style; D012964:Sodium / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D049994:Sodium Potassium Chloride Symporter Inhibitors; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D012964:Sodium; D005947:Glucose
keywords: Diuretics; glucose handling; hypertension; sodium balance