ArticleThe Journal of endocrinology2014
Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.
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Article in The Journal of endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 26 citations in OpenAlex.
- Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia.Nature communications · 2025Article
- Exercise and inactivity as modifiers of β cell function and type 2 diabetes risk.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Review
- Human and mouse muscle transcriptomic analyses identify insulin receptor mRNA downregulation in hyperinsulinemia-associated insulin resistance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Characteristics of the New Insulin-Resistant Zebrafish Model.Pharmaceuticals (Basel, Switzerland) · 2021Article
- DPP4 Activity, Hyperinsulinemia, and Atherosclerosis.The Journal of clinical endocrinology and metabolism · 2021Review
- The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis.Journal of nephrology · 2021Review
- Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets.Diabetologia · 2018Article
- Liver-specific reconstitution of CEACAM1 reverses the metabolic abnormalities caused by its global deletion in male mice.Diabetologia · 2017Article
- Hyperactivation of the Insulin Signaling Pathway Improves Intracellular Proteostasis by Coordinately Up-regulating the Proteostatic Machinery in Adipocytes.The Journal of biological chemistry · 2016Article
- Racial/Ethnic Differences in Insulin Resistance and Beta Cell Function: Relationship to Racial Disparities in Type 2 Diabetes among African Americans versus Caucasians.Current obesity reports · 2015Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Xuefeng YangDepartment 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.
Shuang MeiDepartment 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.
Haihua GuDepartment 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.
Huailan GuoDepartment 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.
Longying ZhaDepartment 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.
Junwei CaiDepartment 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.
Xuefeng LiDepartment 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.
Zhenqi LiuDepartment 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.
Wenhong CaoDepartment 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
University of North Carolina at Chapel Hill · USNutrition Sciences (Belgium) · BEHuazhong University of Science and Technology · CNHubei University of Medicine · CN
Funding
p38 MAPK regulation of hepatic gluconeogenesis and lipogenesisR01DK076039 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CAO, WENHONG · 2007 to 2011
$1.5MNIDDK NIH HHS R01DK076039
Abstract
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 β-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 β-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.
Indexed as
DietAnimalsBlood GlucoseBody WeightCell Line, TumorCells, CulturedCholesterolCricetinaeCytokinesDiabetes Mellitus, Type 2FatsHepatocytesHypoglycemic AgentsInsulin GlargineInsulin, Long-ActingInsulinomaBlood GlucoseCholesterolCytokinesFatsHypoglycemic AgentsInsulin GlargineInsulin, Long-ActingLipidscholesterol synthesisdiabetesglargineinsulininsulin resistanceT2DM
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