Effect of aging on islet beta-cell function and its mechanisms in Wistar rats

Gu, Zhaoyan; Du, Yingzhen; Liu, Yu; Ma, Lian; Li, Lin; Gong, Yanping; Tian, Hui; Li, Chunlin

doi:10.1007/s11357-011-9312-7

Cited by 28 publications

(34 citation statements)

References 41 publications

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“…In particular, aged mice were insulin-resistant and glucoseintolerant, although intolerance was only observed when aged mice were forced to release more insulin; for example, after a higher glucose load (37,38). Our results concur with those of several previous studies (3,5,6,39) but contrast with studies reporting insulin secretory defects with age (1,2,4,8). The discrepancies in the literature may be explained by the confounding influence of the systemic environment (10).…”

Section: Discussionsupporting

confidence: 82%

“…Age-dependent dysfunction of islets and the concomitant dysregulation of blood glucose levels increase the risk for type 2 diabetes (1), which in turn contributes to other age-related chronic diseases. In general, it has been assumed that aging causes an intrinsic dysfunction of the insulin-secreting beta cells through reduced proliferative capacity and/or defective insulin secretion (1)(2)(3)(4)(5)(6)(7)(8)(9). However, there have been numerous reports that age-dependent impairment of glucose homeostasis is not just a result of intrinsic, age-dependent dysfunction of islets but is also caused by systemic factors.…”

mentioning

confidence: 99%

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Young capillary vessels rejuvenate aged pancreatic islets

Almaça

Molina

Drigo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.A ging leads to progressive decline of various homeostatic processes in mammals, including a deteriorating regulation of blood glucose levels. Pancreatic islets are small organs composed of endocrine cells that secrete the major hormones insulin, glucagon, and somatostatin, which play a key role in regulating blood glucose levels. Age-dependent dysfunction of islets and the concomitant dysregulation of blood glucose levels increase the risk for type 2 diabetes (1), which in turn contributes to other age-related chronic diseases. In general, it has been assumed that aging causes an intrinsic dysfunction of the insulin-secreting beta cells through reduced proliferative capacity and/or defective insulin secretion (1-9). However, there have been numerous reports that age-dependent impairment of glucose homeostasis is not just a result of intrinsic, age-dependent dysfunction of islets but is also caused by systemic factors. For example, islet function may be compromised by age-related increases in adiposity (10, 11) and by bloodborne factors (12), or it could be affected indirectly by agerelated deficiencies in vascular remodeling (13). Thus, the replicative decline of old pancreatic beta cells can be attributed to systemic factors (12). Recent studies identified factors present in young blood that reverse age-related cognitive impairments and induce vascular remodeling and regeneration in the brain and skeletal muscle (14-16), but so far it has not been feasible to discriminate systemic influences from aging factors intrinsic to islet endocrine cells. Here we address the long-standing question of whether the age-dependent impairment of glucose homeostasis is caused by intrinsic, age-dependent dysfunction of islets or by systemic aging factors.Our strategy to discern age-related intrinsic changes in islet function was to study islets from young mature (2 mo) and aged (18 mo) mice and to fol...

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Young capillary vessels rejuvenate aged pancreatic islets

Almaça

Molina

Drigo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

View full text Add to dashboard Cite

show abstract

“…In addition, aging might have a significant influence on pancreatic β cell function. Our previous study suggested that β-islet cell function decreased gradually with age (16), and a significant reduction in proliferation and an increase in the frequency of apoptotic β cells were detected in the islets of elderly rats. In a study by Tschen et al (17), the β cell proliferation and the capacity of β cells to regenerate were confirmed to decline with age.…”

Section: Discussionmentioning

confidence: 96%

Influence of Glycemic Variability on the HbA1c Level in Elderly Male Patients with Type 2 Diabetes

Feng

et al. 2012

Intern. Med.

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Objective To investigate the influence of glycemic variability on the HbA1c level in elderly male patients with type 2 diabetes (T2DM). Methods The 24-h glucose profiles were obtained using a continuous glucose monitoring system in 291 elderly male type 2 diabetic patients. The relationship between the glycemic variability and HbA1c level was assessed in these patients. Results The mean amplitude of glycemic excursions (MAGE) in patients with HbA1c " 7.0% was significantly higher than in patients with HbA1c <7.0% (4.33±1.67 vs. 3.48±1.46 mmol/L, p<0.001). A simple (Pearson's) correlation analysis indicated that the MAGE was significantly correlated with the HbA1c (r= 0.229, p<0.001). Compared with the lowest quartile, the highest quartile of the MAGE was associated with a significantly increased risk of having a HbA1c " 7.0% after multiple adjustments (p for trend <0.001). Conclusion The glycemic variability had a significant influence on the HbA1c level in elderly male patients with T2DM. The present data suggests that patients with higher glycemic variability might have higher HbA1c levels.

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“…Group I (4M group): 4 months old rats (similar to 14 years of age in humans) [34] without swim exercise training. Group II (4ME group): 4 months old rats (similar to 14 years of age in humans) with swim exercise training for 6 weeks [35] .…”

Section: Experimental Designmentioning

confidence: 99%

“…Group IV (14M-EX group): 14 months old rats (equivalent to 50 years of age in humans) with swim exercise training for 6 weeks [35] . Group V (24M group): 24 months old rats (approximately 84 years of age in humans) [34] without swim exercise training. Group VI (24M-EX group): 24 months old rats (approximately 84 years of age in humans) with swim exercise training for 6 weeks [35] .…”

Section: Experimental Designmentioning

confidence: 99%

Exercise Training Prevents Age-induced Insulin Resistance in Rats: Effect on Circulating Catecholamines, Inflammatory Cytokines and Skeletal Muscle Glut4 Transporters

El-Gohary¹

2017

Am. J. Biomed. Sci.

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The incidence of insulin resistance increases with age. This work tested the effect of exercise on ageinduced insulin resistance and the possible involved mechanisms. Six groups of rats were used: 4 months old, 14 months old and 24 months old, either with and without exercise training. Swimming exercise training was performed 2h/day, 5days/week for 6 weeks. Insulin resistance was assessed by measuring serum glucose, serum insulin and homeostasis model assessment of insulin resistance (HOMA-IR) index. Serum levels of catecholamines, inflammatory cytokines and total antioxidant capacity (TAC) together with skeletal muscle Glut4 mRNA expression were assessed. Aged rats developed insulin resistance associated with increased serum catecholamines and inflammatory cytokine levels, decreased serum TAC and suppression of skeletal muscle Glut4 expressions. Exercise training reversed the developed insulin resistance and restored the values of catecholamines, inflammatory cytokines and skeletal muscle Glut4; however, it did not modify TAC. It was concluded that exercise could reverse aging-induced insulin resistance in rats by decreasing catecholamines and inflammatory cytokines production and also by increasing Glut4 expression in skeletal muscles.

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Effect of aging on islet beta-cell function and its mechanisms in Wistar rats

Cited by 28 publications

References 41 publications

Young capillary vessels rejuvenate aged pancreatic islets

Young capillary vessels rejuvenate aged pancreatic islets

Influence of Glycemic Variability on the HbA1c Level in Elderly Male Patients with Type 2 Diabetes

Exercise Training Prevents Age-induced Insulin Resistance in Rats: Effect on Circulating Catecholamines, Inflammatory Cytokines and Skeletal Muscle Glut4 Transporters

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