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

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Abstract

Type 2 diabetes mellitus is characterized by islet β-cell dysfunction and its incidence increases with age. However, the mechanisms underlying the effect of aging on islet β-cell function are not fully understood. We characterized β-cell function in 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats, and found that islet β-cell function decreased gradually with age. Old rats displayed oral glucose intolerance and exhibited a decrease in glucose-stimulated insulin release (GSIR) and palmitic acid-stimulated insulin release (PSIR). Furthermore, total superoxide dismutase (T-SOD), CuZn superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activity decreased, whereas serum malondialdehyde (MDA) levels increased in the older rats. Moreover, we detected a significant reduction in β-cell proliferation and an increase in the frequency of apoptotic β-cells in the islets of rats in the old group. Finally, Anxa1 expression in the islets of old rats was significantly upregulated. These data provide new insights into the development of age-related β-cell dysfunction in rats.

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Abbreviations

GSIR:

Glucose-stimulated insulin release

PSIR:

Palmitic acid-stimulated insulin release

GIR:

Glucose infusion rate

CVBG :

Blood glucose coefficient of variation

CVGIR :

GIR coefficient of variation

OGTT:

Oral glucose tolerance test

IRT:

Insulin release test

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

PCNA:

Proliferating cell nuclear antigen

FBG:

Fasting blood glucose

BG peak time:

Time when blood glucose level was at peak

BG peak:

Value of blood glucose level at peak

OGTT2hPG:

Plasma glucose at 120 min post-oral glucose

AUCg:

Area under the curve for glucose throughout the 120 min period

FINS:

Fasting blood insulin

INS peak time:

Time when blood insulin level was at peak

INS peak:

Value of blood insulin level at peak

AUCi:

Area under the curve for insulin throughout the 120-min period

AUCi/g:

Area ratio under the curve for insulin/glucose

ΔI 10/ΔG 10 :

ΔI 10/ΔG 10 = (10 min insulin value −0 min insulin value)/(10 min glucose value −0 min glucose value) (Alvarsson et al. 2005)

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Acknowledgements

This work was supported by grants from the National Nature Science Foundation of China to C.L.L. (no. 38073412) and from the National Nature Science Foundation of China to Y.L. (no. 30801201).

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Authors and Affiliations

  1. Department of Geriatric Endocrinology, PLA General Hospital, Beijing, China

    Zhaoyan Gu, Yingzhen Du, Yu Liu, Lichao Ma, Lin Li, Yanping Gong, Hui Tian & Chunlin Li

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  1. Zhaoyan Gu
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  2. Yingzhen Du
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  3. Yu Liu
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  4. Lichao Ma
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  5. Lin Li
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  6. Yanping Gong
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  7. Hui Tian
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  8. Chunlin Li
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Correspondence to Yu Liu or Chunlin Li.

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Z. Gu and Y. Du made equal contributions to this study.

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Gu, Z., Du, Y., Liu, Y. et al. Effect of aging on islet beta-cell function and its mechanisms in Wistar rats. AGE 34, 1393–1403 (2012). https://doi.org/10.1007/s11357-011-9312-7

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  • DOI: https://doi.org/10.1007/s11357-011-9312-7

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