Effects of aging and insulin resistant states on protein anabolic responses in older adults

Effects of aging and insulin resistant states on protein anabolic responses in older adults Insulin is the principal postprandial anabolic hormone and resistance to its action could contribute to sarcopenia. We developed different types of hyperinsulinemic clamp protocols to measure simultaneously glucose and protein metabolism in insulin resistant states (older adults, obesity, diabetes, etc.). To define effects of healthy aging in response to insulin, we employed the hyperinsulinemic, euglycemic and isoaminoacidemic (HYPER-1) clamp. The net whole-body anabolic (protein balance) response to hyperinsulinemia was lower in the elderly vs young (p = 0.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p < 0.001), indicating insulin resistance of protein metabolism concurrent with that of glucose. Differences in insulin resistance due to aging were observed predominantly in men, with older ones exhibiting significant lower anabolism compared with young ones. As most of the anabolism occurs during feeding, we studied the fed-state metabolic responses with aging using the hyperinsulinemic, hyperglycemic and hyperaminoacidemic clamp, including muscle biopsies. Older women showed comparable whole-body protein anabolic responses and stimulation of mixed-muscle protein synthesis by feeding to the young. The responses of skeletal muscle insulin signaling through the Akt-mTORC1 pathway were also unaltered, and therefore consistent with muscle protein synthesis results. Given that type 2 diabetes infers insulin resistance of protein metabolism with aging, we studied 10 healthy, 8 obese, and 8 obese type 2 diabetic elderly women using the HYPER-1 clamp. When compared to the group of young lean women to define the effects of obesity and diabetes with aging, whole-body change in net protein balance with hyperinsulinemia was similarly blunted in obese and diabetic older women. However, only elderly obese women with diabetes had lower net balance than lean older women. We conclude that with usual aging, the blunted whole-body anabolic response in elderly subjects is mediated by the failure of insulin to stimulate protein synthesis to the same extent as in the young, especially in men. This blunted response can be overcome at the whole-body and muscle levels during an intravenous fed state supplying a generous amount of protein, in active healthy elderly women. Obese elderly women with and without type 2 diabetes have insulin resistance of protein anabolism at the whole-body level, but this resistance is worsened with diabetes when glucose metabolism is further impaired. More investigation is needed to determine the exact role of insulin in promoting anabolism with aging. The findings from our group are relevant for the field of sarcopenia research as they provide a rationale to offer low cost nutritional interventions for overcoming this detrimental condition associated with aging and diabetes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Gerontology Elsevier

Effects of aging and insulin resistant states on protein anabolic responses in older adults

Loading next page...
 
/lp/elsevier/effects-of-aging-and-insulin-resistant-states-on-protein-anabolic-9UB2CCNGMV
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
0531-5565
eISSN
1873-6815
D.O.I.
10.1016/j.exger.2018.04.025
Publisher site
See Article on Publisher Site

Abstract

Insulin is the principal postprandial anabolic hormone and resistance to its action could contribute to sarcopenia. We developed different types of hyperinsulinemic clamp protocols to measure simultaneously glucose and protein metabolism in insulin resistant states (older adults, obesity, diabetes, etc.). To define effects of healthy aging in response to insulin, we employed the hyperinsulinemic, euglycemic and isoaminoacidemic (HYPER-1) clamp. The net whole-body anabolic (protein balance) response to hyperinsulinemia was lower in the elderly vs young (p = 0.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p < 0.001), indicating insulin resistance of protein metabolism concurrent with that of glucose. Differences in insulin resistance due to aging were observed predominantly in men, with older ones exhibiting significant lower anabolism compared with young ones. As most of the anabolism occurs during feeding, we studied the fed-state metabolic responses with aging using the hyperinsulinemic, hyperglycemic and hyperaminoacidemic clamp, including muscle biopsies. Older women showed comparable whole-body protein anabolic responses and stimulation of mixed-muscle protein synthesis by feeding to the young. The responses of skeletal muscle insulin signaling through the Akt-mTORC1 pathway were also unaltered, and therefore consistent with muscle protein synthesis results. Given that type 2 diabetes infers insulin resistance of protein metabolism with aging, we studied 10 healthy, 8 obese, and 8 obese type 2 diabetic elderly women using the HYPER-1 clamp. When compared to the group of young lean women to define the effects of obesity and diabetes with aging, whole-body change in net protein balance with hyperinsulinemia was similarly blunted in obese and diabetic older women. However, only elderly obese women with diabetes had lower net balance than lean older women. We conclude that with usual aging, the blunted whole-body anabolic response in elderly subjects is mediated by the failure of insulin to stimulate protein synthesis to the same extent as in the young, especially in men. This blunted response can be overcome at the whole-body and muscle levels during an intravenous fed state supplying a generous amount of protein, in active healthy elderly women. Obese elderly women with and without type 2 diabetes have insulin resistance of protein anabolism at the whole-body level, but this resistance is worsened with diabetes when glucose metabolism is further impaired. More investigation is needed to determine the exact role of insulin in promoting anabolism with aging. The findings from our group are relevant for the field of sarcopenia research as they provide a rationale to offer low cost nutritional interventions for overcoming this detrimental condition associated with aging and diabetes.

Journal

Experimental GerontologyElsevier

Published: Jul 15, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off