SGK1 inhibitor reverses hyperglycemia partly through decreasing glucose absorption.
This study investigates the effectiveness and mechanisms of a serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibitor in counteracting hyperglycemia. In an in vivo experiment, we demonstrated that after an 8-week treatment with an SGK1 inhibitor, the fasting blood glucose and HbA1c level significantly decreased in db/db mice. RT-PCR and western blot analyses revealed that intestinal SGK1 and sodium glucose co-transporter 1 (SGLT1) expression were enhanced in db/db mice. Treatment with an SGK1 inhibitor decreased excessive SGLT1 expression in the intestine of db/db mice. In vitro experiments with intestinal IEC-6 cells showed that the co-administration of an SGK1 inhibitor partly reversed the SGLT1 expression and glucose absorption that were induced by dexamethasone. In conclusion, this study revealed that the favorable effect of an SGK1 inhibitor on hyperglycemia is partly due to decreased glucose absorption through SGLT1 in the small intestine. These data collectively suggest that SGK1 may be a potent target for the treatment of diabetes and other metabolic disorders.
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China.
Ping
P
Li
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China.
Yan
Y
Hao
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China.
Feng-Hui
FH
Pan
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China.
Min
M
Zhang
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China.
Jian-Qiang
JQ
Ma
Department of EndocrinologyDrum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China zhudalong@nju.edu.cn.
Da-Long
DL
Zhu
D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose; D002460:Cell Line; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D000099184:Serum-Glucocorticoid Regulated Kinases
D015415:Biomarkers; D001786:Blood Glucose; D005947:Glucose; D017874:Immediate-Early Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases
IEC-6 intestinal cells; serum- and glucocorticoid-inducible kinase 1 (SGK1); small intestine; sodium glucose co-transporter 1 (SGLT1)