Ongoing β-Cell Turnover in Adult Nonhuman Primates Is Not Adaptively Increased in Streptozotocin-Induced Diabetes

Saisho, Yoshifumi; Manesso, Erica; Butler, Alexandra E.; Galasso, Ryan; Kavanagh, Kylie; Flynn, Mickey; Zhang, Li; Clark, Paige B.; Gurlo, Tatyana; Toffolo, Gianna; Cobelli, Claudio; Wagner, Janice D.; Butler, Peter C.

doi:10.2337/db09-1368

Cited by 38 publications

(32 citation statements)

References 37 publications

(44 reference statements)

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“…Aging is thought to be associated with reduced capacity to regenerate b-cells, as suggested by studies involving rodents (13)(14)(15) and humans (16)(17)(18). On the one hand, for example, the b-cell toxin streptozotocin, partial pancreatectomy, or exendin-4 were more effective in stimulating b-cell proliferation in younger mice (younger than 12 months old) than in older mice (13)(14)(15)19). On the other hand, the age-associated decline in b-cell function in older rats has been shown to be reversible with glucagonlike peptide 1 (GLP-1; exendin) treatment (20), suggesting stimulation of b-cell regeneration (21).…”

Section: Effects Of Agingmentioning

confidence: 99%

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

2017

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Nearly a quarter of older adults in the U.S. have type 2 diabetes, and this population is continuing to increase with the aging of the population. Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. The usual defects contributing to type 2 diabetes are further complicated by the natural physiological changes associated with aging as well as the comorbidities and functional impairments that are often present in older people. This paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population.Diabetes is one of the leading chronic medical conditions among older adults, with high risk for vascular comorbidities such as coronary artery disease, physical and cognitive function impairment, and mortality. Despite decades of effort to prevent diabetes, diabetes remains an epidemic condition with particularly high morbidity affecting older adults. In fact, nearly 11 million people in the U.S. aged 65 years or older (more than 26% of adults aged 65 years or older) meet current American Diabetes Association criteria for diabetes (diagnosed and undiagnosed), accounting for more than 37% of the adult population with diabetes (1). At the same time, adults 65 years or older are developing diabetes at a rate nearly three-times higher than younger adults: 11.5 per 1,000 people compared with 3.6 per 1,000 people among adults aged 20-44 years old (1). However, increasing research in diabetes and aging has improved our understanding of the pathophysiology of diabetes and its association with aging and led to the development of a number of antihyperglycemic medications. The mechanism of diabetes complications has been previously reviewed (2). The current paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population. PATHOPHYSIOLOGY OF TYPE 2 DIABETESType 2 diabetes is by far the most prevalent form of diabetes in older adults and is an age-related disorder. The criteria for diagnosing diabetes are the same for all age groups because the risks of diabetes-related complications are associated with hyperglycemia over time across all age groups (3). Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. These factors contribute to hyperglycemia through effects on both b-cell insulin secretory capacity and on tissue sensitivity to insulin. The occurrence of type 2 diabetes in an older person is complicated by the comorbidities and functional impairments associated with aging.Hyperglycemia develops in type 2 diabetes when there is an imbalance of glucose production (i.e., hepatic glucose production during fasting) and glucose intake (i.e.,

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Section: Effects Of Agingmentioning

confidence: 99%

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

2017

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“…Regeneration of β cells may be similarly restricted in non-human primates. Butler and colleagues recently investigated the β cell regenerative capacity of middle-aged velvet monkeys in response to streptozotocin (40). Although streptozotocin reliably induced diabetes, β cell replication was not increased in the monkeys.…”

Section: Aging Impairs Human β Cell Functionmentioning

confidence: 99%

The role of aging upon β cell turnover

2013

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Preservation and regeneration of β cell endocrine function is a long-sought goal in diabetes research. Defective insulin secretion from β cells underlies both type 1 and type 2 diabetes, thus fueling considerable interest in molecules capable of rebuilding β cell secretion capacity. Though early work in rodents suggested that regeneration might be possible, recent studies have revealed that aging powerfully restricts cell cycle entry of β cells, which may limit regeneration capacity. Consequently, aging has emerged as an enigmatic challenge that might limit β cell regeneration therapies. This Review summarizes recent data regarding the role of aging in β cell regeneration and proposes models explaining these phenomena.

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“…These cells, located within the islets of Langerhans, display a slow turnover rate (3,4). Conditions such as pregnancy and obesity are associated with a diminished sensitivity of insulin target tissues and a consequent rise in the insulin demand that is compensated for by an increase in the number and secretory activity of β cells (2,(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

Jacovetti¹,

Abderrahmani²,

Parnaud³

et al. 2012

J. Clin. Invest.

157

168

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Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.

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Ongoing β-Cell Turnover in Adult Nonhuman Primates Is Not Adaptively Increased in Streptozotocin-Induced Diabetes

Cited by 38 publications

References 37 publications

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

The role of aging upon β cell turnover

MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity

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