Abstract
BackgroundDipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis.MethodWe examined whether weekly DPP4 inhibitor omarigliptin (OMG) can improve liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Further, we investigated the effects of OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH).ResultsIn NAFLD patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c or body mass index. In the NASH patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Slight but clear improvements in intrahepatic fat deposition and fibrosis appeared to be seen on diagnostic ultrasonography.ConclusionWeekly administration of the DPP4 inhibitor OMG in ameliorating hepatic insulin resistance may cause beneficial effects in liver with NAFLD/NASH.
Highlights
Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and a hepatokine
In non-alcoholic fatty liver disease (NAFLD) patients, OMG significantly decreased levels of aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein, while no significant change was seen in hemoglobin A1c or body mass index
In the nonalcoholic steatohepatitis (NASH) patient, liver function improved markedly, and levels of the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and high-sensitivity C-reactive protein (hsCRP)
Summary
Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides, and a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis. Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides through the removal of N-terminal dipeptides [1]. A direct association exists between DPP4 activity and insulin resistance in humans [3]. Evidence suggests that obesity in mice stimulates hepatocytes to synthesize and secrete DPP4, in turn promoting inflammation of adipose tissue macrophages and insulin resistance. Silencing expression of DPP4 on hepatocytes suppressed inflammation of visceral adipose tissue and insulin resistance, but this effect did not occur with sitagliptin, an orally administered DPP4 inhibitor [4].
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