Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Jun;3(6):565-75.
doi: 10.18632/aging.100350.

Type 2 diabetes and the aging pancreatic beta cell

Uma Gunasekaran  1 , Maureen Gannon
Affiliations
Review

Type 2 diabetes and the aging pancreatic beta cell

Uma Gunasekaran et al. Aging (Albany NY). 2011 Jun.

Abstract

The incidence of and susceptibility to Type 2 diabetes increases with age, but the underlying mechanism(s) within beta cells that contribute to this increased susceptibility have not been fully elucidated. Here we review how aging affects the proliferative and regenerative capacity of beta cells and how this impacts beta cell mass. In addition we review changes that occur in beta cell function with age. Although we focus on the different rodent models that have provided insight into the characteristics of the aging beta cell, the limited knowledge from non-rodent models is also reviewed. Further studies are needed in order to identify potential beta cell targets for preventing or slowing the progression of diabetes that occurs with age.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Summary of the effects of age on various beta cell parameters.
Multiple factors influence the beta cell as it ages. Each of the factors listed here is discussed in more detail in the text. This graph is a representation of how these parameters change with age. The actual kinetics of each of these changes has not been fully elucidated.
Figure 2
Figure 2. Effects of p16Ink4a on Cdk4/6.
(A) The p16Ink4a cell cycle inhibitor sequesters Cdk4 or Cdk6, preventing interactions with cyclin D proteins, and thus phosphorylation of pRB. Hypophosphorylated pRB sequesters the E2F transcription factor, thus thus inihibiting cell cycle progression. (B) In the absence of p16Ink4a, cyclin D forms a productive complex with either Cdk4 or Cdk6 and phosphorylates RB. This phosphorylation releases the E2F transcription factor, facilitating the G1 to S phase cell cycle transition. Thus, in the presence of elevated p16Ink4a, such as with aging, there is cell cycle arrest and cellular senescence. Adapted from [32]
Figure 3
Figure 3. Effects of p19Arf on the cell cycle.
In the absence of p19Arf, p53 is ubiquitinized and subsequently degraded by the proteosome. p19Arf inhibits the ubiquitin-modulated effect of p53 by MDM2. p19Arf inhibits ubiquitin-mediated p53 degradation resulting in induction of p21 and subsequently cell cycle arrest. Adapted from [75] and [76]
Figure 4
Figure 4. BMI-1 and Ezh2: Effects on transcription.
(A) The Ezh2 (Enhancer of zeste homologue 2) component of the PRC2 (Polycomb repressor complex 2) complex methylates lysine (K) 27 of histone H3 (H3K27). This methylation process recruits the PRC1 (Polycomb repressor complex 1) complex. (B) The Ring1A and Ring1B components of this complex ubiquitylate H2AK119. This ubiquitylation causes transcriptional repression, for example at the Ink4a/Arf locus. In addition to Ezh2, the PRC2 complex contains EED (embryonic ectoderm development) and Suz12 (suppressor of zeste homologue 12). The PRC1 complex contains BMI-1, Ring 1A, Ring 1B, PH1 (Polycomb homologue 1), and PH1 (Polyhomeotic homologue 1). Adapted from [77].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E. Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab. 1999;84:863–8. - PubMed
    1. Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE, Geiss LS, Gregg EW. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002. Diabetes Care. 2006;29:1263–8. - PubMed
    1. Cowie CC, Rust KF, Ford ES, Eberhardt MS, Byrd-Holt DD, Li C, Williams DE, Gregg EW, Bainbridge KE, Saydah SH, Geiss LS. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care. 2009;32:287–94. - PMC - PubMed
    1. Statistics FIFoA-R Older Americans 2010: Key Indicators of Well-Being. 2010. http://www.agingstats.gov
    1. Scheen AJ. Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion? Diabetes Metab. 2005;31(Spec No 2):5S27–5S34. - PubMed

Publication types

Substances