Tags

Type your tag names separated by a space and hit enter

Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling.
Am J Physiol Endocrinol Metab 2007; 293(6):E1687-96AJ

Abstract

Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2(Akita) and wild-type mice to measure insulin action and glucose metabolism in vivo. Nonobese Ins2(Akita) mice developed insulin resistance, as indicated by an approximately 80% reduction in glucose infusion rate during clamps. Insulin resistance was due to approximately 50% decreases in glucose uptake in skeletal muscle and brown adipose tissue as well as hepatic insulin action. Skeletal muscle insulin resistance was associated with a 40% reduction in total GLUT4 and a threefold increase in PKCepsilon levels in Ins2(Akita) mice. Chronic phloridzin treatment lowered systemic glucose levels and normalized muscle insulin action, GLUT4 and PKCepsilon levels in Ins2(Akita) mice, indicating that hyperglycemia plays a role in insulin resistance. Echocardiography showed significant cardiac remodeling with ventricular hypertrophy that was ameliorated following chronic phloridzin treatment in Ins2(Akita) mice. Overall, we report for the first time that nonobese, insulin-deficient Ins2(Akita) mice develop type 2 diabetes phenotypes including peripheral and hepatic insulin resistance and cardiac remodeling. Our findings provide important insights into the pathogenesis of metabolic abnormalities and complications affecting type 1 diabetes and lean type 2 diabetes subjects.

Authors+Show Affiliations

Dept. of Cellular and Molecular Physiology, Penn State Univ. College of Medicine, 500 University Dr. (H166 C4600D, Hershey, PA 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17911348

Citation

Hong, Eun-Gyoung, et al. "Nonobese, Insulin-deficient Ins2Akita Mice Develop Type 2 Diabetes Phenotypes Including Insulin Resistance and Cardiac Remodeling." American Journal of Physiology. Endocrinology and Metabolism, vol. 293, no. 6, 2007, pp. E1687-96.
Hong EG, Jung DY, Ko HJ, et al. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab. 2007;293(6):E1687-96.
Hong, E. G., Jung, D. Y., Ko, H. J., Zhang, Z., Ma, Z., Jun, J. Y., ... Kim, J. K. (2007). Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. American Journal of Physiology. Endocrinology and Metabolism, 293(6), pp. E1687-96.
Hong EG, et al. Nonobese, Insulin-deficient Ins2Akita Mice Develop Type 2 Diabetes Phenotypes Including Insulin Resistance and Cardiac Remodeling. Am J Physiol Endocrinol Metab. 2007;293(6):E1687-96. PubMed PMID: 17911348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. AU - Hong,Eun-Gyoung, AU - Jung,Dae Young, AU - Ko,Hwi Jin, AU - Zhang,Zhiyou, AU - Ma,Zhexi, AU - Jun,John Y, AU - Kim,Jae Hyeong, AU - Sumner,Andrew D, AU - Vary,Thomas C, AU - Gardner,Thomas W, AU - Bronson,Sarah K, AU - Kim,Jason K, Y1 - 2007/10/02/ PY - 2007/10/4/pubmed PY - 2008/2/26/medline PY - 2007/10/4/entrez SP - E1687 EP - 96 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 293 IS - 6 N2 - Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2(Akita) and wild-type mice to measure insulin action and glucose metabolism in vivo. Nonobese Ins2(Akita) mice developed insulin resistance, as indicated by an approximately 80% reduction in glucose infusion rate during clamps. Insulin resistance was due to approximately 50% decreases in glucose uptake in skeletal muscle and brown adipose tissue as well as hepatic insulin action. Skeletal muscle insulin resistance was associated with a 40% reduction in total GLUT4 and a threefold increase in PKCepsilon levels in Ins2(Akita) mice. Chronic phloridzin treatment lowered systemic glucose levels and normalized muscle insulin action, GLUT4 and PKCepsilon levels in Ins2(Akita) mice, indicating that hyperglycemia plays a role in insulin resistance. Echocardiography showed significant cardiac remodeling with ventricular hypertrophy that was ameliorated following chronic phloridzin treatment in Ins2(Akita) mice. Overall, we report for the first time that nonobese, insulin-deficient Ins2(Akita) mice develop type 2 diabetes phenotypes including peripheral and hepatic insulin resistance and cardiac remodeling. Our findings provide important insights into the pathogenesis of metabolic abnormalities and complications affecting type 1 diabetes and lean type 2 diabetes subjects. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17911348/Nonobese_insulin_deficient_Ins2Akita_mice_develop_type_2_diabetes_phenotypes_including_insulin_resistance_and_cardiac_remodeling_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00256.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -