Mingyuan Tian1, Zerong Liang1, Rui Liu1, Ke Li1, Xinrong Tan2, Yong Luo1, Mengliu Yang1, Harvest F Gu1, Hua Liu1, Ling Li3, Gangyi Yang3. 1. Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA. 2. Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA. 3. Department of EndocrinologyThe Second Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaDpartment of Endocrinology9th People's Hospital of Chongqing, Chongqong, ChinaDepartment of EndocrinologyChongqing Three Gorges Central Hospital, Chongqing, ChinaDepartment of Molecular Medicine and SurgeryKarolinska Institutet, Karolinska University Hospital, Solna, Stockholm, SwedenDepartment of PediatricsUniversity of Mississippi Medical Center, Jackson, Mississippi, USA liling31@hotmail.com gangyiyang@163.com.
Abstract
OBJECTIVE:Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients. DESIGN AND METHODS: A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations. RESULTS:Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasmaTNF-α level (P<0.05). CONCLUSION: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.
RCT Entities:
OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients. DESIGN AND METHODS: A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations. RESULTS: Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05). CONCLUSION: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.
Authors: Erik E Gómez-Cardona; Eric E Hernández-Domínguez; Aída J Velarde-Salcedo; Alberto-Barrera- Pacheco; Agustín Diaz-Gois; Antonio De León-Rodríguez; Ana P Barba de la Rosa Journal: Sci Rep Date: 2017-04-20 Impact factor: 4.379
Authors: Sang Woo Kim; Jung-Won Choi; Jong Won Yun; In-Sung Chung; Ho Chan Cho; Seung-Eun Song; Seung-Soon Im; Dae-Kyu Song Journal: PLoS One Date: 2019-09-10 Impact factor: 3.240