PMID- 24741073
OWN - NLM
STAT- MEDLINE
DCOM- 20140725
LR  - 20211021
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 221
IP  - 3
DP  - 2014 Jun
TI  - Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice 
      fed on a chow diet.
PG  - 469-80
LID - 10.1530/JOE-14-0117 [doi]
AB  - We have previously shown that insulin plays an important role in the 
      nutrient-induced insulin resistance. In this study, we tested the hypothesis that 
      chronic exposure to excess long-acting insulin (glargine) can cause typical type 
      2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were 
      treated with glargine once a day for 8 weeks, followed by evaluations of food 
      intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, 
      insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative 
      stress level, and cholesterol content in mitochondria in tissues. Cholesterol 
      content in mitochondria and its association with oxidative stress in cultured 
      hepatocytes and beta-cells were also examined. Results show that chronic exposure to 
      glargine caused insulin resistance, hyperinsulinemia, and relative insulin 
      deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic 
      islets, ectopic fat accumulation in liver, oxidative stress in liver and 
      pancreas, and increased cholesterol content in mitochondria of liver and 
      pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 beta-cells 
      to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. 
      Together, our results show that chronic exposure to excess insulin can induce 
      typical T2DM in normal mice fed on a chow diet.
CI  - (c) 2014 The authors.
FAU - Yang, Xuefeng
AU  - Yang X
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of 
      Nutrition and Food HygieneTongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Mei, Shuang
AU  - Mei S
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Gu, Haihua
AU  - Gu H
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Guo, Huailan
AU  - Guo H
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of 
      Nutrition and Food HygieneTongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Zha, Longying
AU  - Zha L
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of 
      Nutrition and Food HygieneTongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Cai, Junwei
AU  - Cai J
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of 
      Nutrition and Food HygieneTongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Li, Xuefeng
AU  - Li X
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Liu, Zhenqi
AU  - Liu Z
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USA.
FAU - Cao, Wenhong
AU  - Cao W
AD  - Department of NutritionGillings School of Global Public Health, Nutrition 
      Research Institute (NRI) at Kannapolis, The University of North Carolina at 
      Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of Nutrition and 
      Food HygieneTongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The University of North 
      Carolina at Chapel Hill, Chapel Hill, North Carolina 27559, USADepartment of 
      Nutrition and Food HygieneTongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, Hubei 430030, People's Republic of ChinaDepartment of 
      Preventive MedicineHubei University of Medicine, Shiyan, Hubei 442000, People's 
      Republic of ChinaDepartment of Nutrition and Food HygieneSchool of Public Health 
      and Tropical Medicine, Southern Medical University, Guangzhou 510515, 
      ChinaDepartment of MedicineTai He Hospital, Hubei University of Medicine, Shiyan, 
      Hubai 442000, ChinaDepartment of Medicine (Endocrinology)University of Virginia 
      Health System, Charlottesville, Virginia 22908, USADepartment of Medicine 
      (Endocrinology and Metabolism)Duke University School of Medicine, Durham, North 
      Carolina 27705, USADepartment of NutritionGillings School of Global Public 
      Health, Nutrition Research Institute (NRI) at Kannapolis, The Univ
LA  - eng
GR  - R01DK076039/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140416
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Fats)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin, Long-Acting)
RN  - 0 (Lipids)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Body Weight/drug effects/physiology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - Cricetinae
MH  - Cytokines/blood
MH  - Diabetes Mellitus, Type 2/blood/chemically induced/*physiopathology
MH  - *Diet
MH  - Fats/metabolism
MH  - Hepatocytes/drug effects/metabolism
MH  - Hypoglycemic Agents/administration & dosage/toxicity
MH  - Insulin Glargine
MH  - Insulin Resistance/*physiology
MH  - Insulin, Long-Acting/*administration & dosage/blood/toxicity
MH  - Insulinoma/metabolism/pathology
MH  - Lipids/blood
MH  - Lipogenesis/drug effects/genetics
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/drug effects
MH  - Pancreas/drug effects/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4045231
OTO - NOTNLM
OT  - T2DM
OT  - cholesterol synthesis
OT  - diabetes
OT  - glargine
OT  - insulin
OT  - insulin resistance
EDAT- 2014/04/18 06:00
MHDA- 2014/07/26 06:00
PMCR- 2014/06/01
CRDT- 2014/04/18 06:00
PHST- 2014/04/18 06:00 [entrez]
PHST- 2014/04/18 06:00 [pubmed]
PHST- 2014/07/26 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - JOE-14-0117 [pii]
AID - JOE140117 [pii]
AID - 10.1530/JOE-14-0117 [doi]
PST - ppublish
SO  - J Endocrinol. 2014 Jun;221(3):469-80. doi: 10.1530/JOE-14-0117. Epub 2014 Apr 16.