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Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

Mohamad M, Mitchell SJ, Wu LE, White MY, Cordwell SJ, Mach J, Solon-Biet SM, Boyer D, Nines D, Das A, Catherine Li SY, Warren A, Hilmer SN, Fraser R, Sinclair DA, Simpson SJ, de Cabo R, Le Couteur DG, Cogger VC - Aging Cell (2016)

Bottom Line: While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown.To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling.Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Ageing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.

No MeSH data available.


Related in: MedlinePlus

(a) Glucose tolerance was maintained despite hyperinsulinemia with old age in mice (n = 8 young and 5 old C57Bl6 mice). (b) The HOMA index was found to be significantly increased with age, reflecting the high insulin levels (n = 6 young and 5 old mice, P = 0.03). (c) There was a significant reduction in hepatic uptake of 14C‐glucose and a trend toward increased uptake by the muscle and the fat with age (n = 8 young and 5 old mice, P < 0.05). (d) 3H‐2‐deoxyglucose incorporation into the fat and the muscle was found to be significantly increased with age (n = 8 young and 5 old mice, P < 0.05).
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acel12481-fig-0002: (a) Glucose tolerance was maintained despite hyperinsulinemia with old age in mice (n = 8 young and 5 old C57Bl6 mice). (b) The HOMA index was found to be significantly increased with age, reflecting the high insulin levels (n = 6 young and 5 old mice, P = 0.03). (c) There was a significant reduction in hepatic uptake of 14C‐glucose and a trend toward increased uptake by the muscle and the fat with age (n = 8 young and 5 old mice, P < 0.05). (d) 3H‐2‐deoxyglucose incorporation into the fat and the muscle was found to be significantly increased with age (n = 8 young and 5 old mice, P < 0.05).

Mentions: Although the old mice were hyperinsulinemic, the glucose tolerance test was not impaired, in fact tended to be lower (Fig. 2a). However, because of the very high insulin levels, the homeostatic model assessment index for insulin resistance (HOMA‐IR), which is calculated from the product of the fasting glucose and insulin levels, was found to be increased by more than twofold in the old mice, indicating the insulin resistance (Fig. 2b).


Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

Mohamad M, Mitchell SJ, Wu LE, White MY, Cordwell SJ, Mach J, Solon-Biet SM, Boyer D, Nines D, Das A, Catherine Li SY, Warren A, Hilmer SN, Fraser R, Sinclair DA, Simpson SJ, de Cabo R, Le Couteur DG, Cogger VC - Aging Cell (2016)

(a) Glucose tolerance was maintained despite hyperinsulinemia with old age in mice (n = 8 young and 5 old C57Bl6 mice). (b) The HOMA index was found to be significantly increased with age, reflecting the high insulin levels (n = 6 young and 5 old mice, P = 0.03). (c) There was a significant reduction in hepatic uptake of 14C‐glucose and a trend toward increased uptake by the muscle and the fat with age (n = 8 young and 5 old mice, P < 0.05). (d) 3H‐2‐deoxyglucose incorporation into the fat and the muscle was found to be significantly increased with age (n = 8 young and 5 old mice, P < 0.05).
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4933657&req=5

acel12481-fig-0002: (a) Glucose tolerance was maintained despite hyperinsulinemia with old age in mice (n = 8 young and 5 old C57Bl6 mice). (b) The HOMA index was found to be significantly increased with age, reflecting the high insulin levels (n = 6 young and 5 old mice, P = 0.03). (c) There was a significant reduction in hepatic uptake of 14C‐glucose and a trend toward increased uptake by the muscle and the fat with age (n = 8 young and 5 old mice, P < 0.05). (d) 3H‐2‐deoxyglucose incorporation into the fat and the muscle was found to be significantly increased with age (n = 8 young and 5 old mice, P < 0.05).
Mentions: Although the old mice were hyperinsulinemic, the glucose tolerance test was not impaired, in fact tended to be lower (Fig. 2a). However, because of the very high insulin levels, the homeostatic model assessment index for insulin resistance (HOMA‐IR), which is calculated from the product of the fasting glucose and insulin levels, was found to be increased by more than twofold in the old mice, indicating the insulin resistance (Fig. 2b).

Bottom Line: While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown.To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling.Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Ageing and Alzheimers Institute, Centre for Education and Research on Ageing, University of Sydney and Concord Hospital, Sydney, NSW, Australia.

No MeSH data available.


Related in: MedlinePlus