Advancing age is associated with an increased risk of impaired glucose tolerance and the development of type 2 diabetes. Because these disorders are themselves risk factors for diseases associated with significant morbidity and mortality, new approaches to maintain glucose homeostasis in the aged are urgently needed. Although beta cell dysfunction has been implicated as a contributing factor to disordered glucose homeostasis in the aged, the nature of the beta cell defects that emerge in older individuals has not been carefully studied. Thus, the objective of the proposed study is to identify the precise nature of the beta cell defects that emerge with age and obesity, and gain insight as to whether these defects can be mitigated by known interventions that extend healthspan.

Public Health Relevance

As the population ages and diet-induced obesity spreads, the number of people suffering from type 2 diabetes and its complications is also increasing. The project proposed here, which will help to identify new ways to treat type 2 diabetes in the elderly, will improve health in the elderly and reduce the significant burden that diabetes treatment places on the healthcare system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
3R21AG050135-02S1
Application #
9519215
Study Section
Program Officer
Fridell, Yih-Woei
Project Start
2016-05-01
Project End
2019-04-30
Budget Start
2017-09-01
Budget End
2019-04-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Green, Cara L; Lamming, Dudley W (2018) Regulation of metabolic health by essential dietary amino acids. Mech Ageing Dev :
Hennings, Thomas G; Chopra, Deeksha G; DeLeon, Elizabeth R et al. (2018) In Vivo Deletion of ?-Cell Drp1 Impairs Insulin Secretion Without Affecting Islet Oxygen Consumption. Endocrinology 159:3245-3256
Yu, Deyang; Yang, Shany E; Miller, Blake R et al. (2018) Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms. FASEB J 32:3471-3482
Cummings, Nicole E; Williams, Elizabeth M; Kasza, Ildiko et al. (2018) Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol 596:623-645
Sharick, Joe T; Favreau, Peter F; Gillette, Amani A et al. (2018) Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon. Sci Rep 8:5456
Waqas, Syed F Hassnain; Hoang, Anh Cuong; Lin, Ya-Tin et al. (2017) Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages. J Clin Invest 127:2842-2854
Cummings, Nicole E; Lamming, Dudley W (2017) Regulation of metabolic health and aging by nutrient-sensitive signaling pathways. Mol Cell Endocrinol 455:13-22
Linnemann, Amelia K; Blumer, Joseph; Marasco, Michelle R et al. (2017) Interleukin 6 protects pancreatic ? cells from apoptosis by stimulation of autophagy. FASEB J 31:4140-4152
Kim, So Yoon; Lee, Ji-Hyeon; Merrins, Matthew J et al. (2017) Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary ?-Cell Dysfunction to Progressive Depletion of ?-Cell Mass and Diabetes. J Biol Chem 292:3841-3853
Lamming, Dudley W; Baar, Emma L; Arriola Apelo, Sebastian I et al. (2017) Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J mice. Nutr Healthy Aging 4:239-245

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