The Altered Metabolic Homeostasis in Middle Aged

Mini Review Volume 3 Issue 2  January 2018

OAJ Gerontol & Geriatric Med Copyright © All rights are reserved by Vinod Nikhra

The Altered Metabolic Homeostasis in Middle Aged and Elderly: Aging and Other Determinants of Insulin Secretion, Action and Resistance Vinod Nikhra* ‡‹‘”Š‹‡ˆ‡†‹…ƒŽˆϔ‹…‡”ƒ†‘•—Ž–ƒ–ǡ‡’ƒ”–‡–‘ˆ‡†‹…‹‡ǡ‹†—ƒ‘‘•’‹–ƒŽƒ†‡†‹…ƒŽ‘ŽŽ‡‰‡ǡ †‹ƒ Submission: January 25, 2018; Published: January 31, 2018 *Corresponding author: Vinod Nikhra, Department of Medicine, Hindu Rao Hospital and NDMC Medical College, New Delhi, India, Email:

Abstract Metabolic Homeostasis and Aging: Š‡”‡ ‹• ƒ …Ž‘•‡ ”‡Žƒ–‹‘•Š‹’ „‡–™‡‡ Š‘‡‘•–ƒ•‹• ƒ† ‡–ƒ„‘Ž‹•Ǥ Š‡ ‹ƒ„‹Ž‹–› –‘ ƒ‹–ƒ‹ Š‘‡‘•–ƒ•‹•Ž‡ƒ†•Š‘‡‘•–ƒ–‹…‹„ƒŽƒ…‡ǡ”‡•—Ž–‹‰‹˜ƒ”‹‘—•‡–ƒ„‘Ž‹…†‹•‘”†‡”•ƒ††‹•‡ƒ•‡•–ƒ–‡•‹…Ž—†‹‰†‹ƒ„‡–‡•Ǥ‰‹‰‹•ƒ‹’‘”–ƒ– ”‹•ˆƒ…–‘”ˆ‘”‡–ƒ„‘Ž‹…†‹•‘”†‡”•‹…Ž—†‹‰‘„‡•‹–›ǡ‹’ƒ‹”‡†‰Ž—…‘•‡–‘Ž‡”ƒ…‡ǡƒ†›’‡ʹ‹ƒ„‡–‡•‡ŽŽ‹–—•ȋʹȌǤ –ƒˆˆ‡…–•…ƒ”„‘Š›†”ƒ–‡ Š‘‡‘•–ƒ•‹•„›ƒŽ–‡”‹‰’ƒ…”‡ƒ–‹…Ⱦ…‡ŽŽˆ—…–‹‘ǡȾ…‡ŽŽƒ••ǡ‹•—Ž‹•‡…”‡–‹‘ƒ†‹•—Ž‹•‡•‹–‹˜‹–›ǡƒ†’”‡†‹•’‘•‡•ˆ‘”‹•—Ž‹”‡•‹•–ƒ…‡ ȋ Ȍǡ‹’ƒ‹”‡†‰Ž—…‘•‡–‘Ž‡”ƒ…‡ƒ††‹ƒ„‡–‡•Ǥ

•Ž‡–• Ⱦ ‡ŽŽ• ƒ† •—Ž‹ ‡…”‡–‹‘ǣ •—Ž‹ ‹• –Š‡ ƒŒ‘” Š‘”‘‡ ˆ‘” ”‡‰—Žƒ–‹‰ ‰Ž—…‘•‡ Š‘‡‘•–ƒ•‹•Ǥ –• •‡…”‡–‹‘ ˆ”‘ Ⱦ …‡ŽŽ• ‹• ƒ …‘’Ž‡š’”‘…‡••ƒ†‹˜‘Ž˜‡•–Š‡‹–‡‰”ƒ–‹‘‘ˆ˜ƒ”‹‘—••–‹—Ž‹Ǥ Ž—…‘•‡‹•–”ƒ•’‘”–‡†‹–‘–Š‡Ⱦ…‡ŽŽ•ǡ—†‡”‰‘‡•‘š‹†ƒ–‹‘–‘„—‹Ž†Ǧ—’ ”‡“—‹”‡† ˆ‘” ‹•—Ž‹ •‡…”‡–‹‘ –Š”‘—‰Š ‡š‘…›–‘•‹•Ǥ Š‡ ƒ‰‹‰ ƒˆˆ‡…–• ˜ƒ”‹‘—• ƒ•’‡…–• ‘ˆ ȾǦ…‡ŽŽ ƒ•• ƒ† ˆ—…–‹‘ †‡…Ž‹‡ ™‹–Š ƒ‰‡ǡ –Š‡”‡ ‹• †‡…”‡ƒ•‡† ‡š’”‡••‹‘ƒ††‡ˆ‡…–•‹‹•—Ž‹•‡…”‡–‹‘ǡ•‡•‹–‹˜‹–›ƒ†ƒ…–‹‘ǤŠ‡”‡‹•‹’ƒ‹”‡†‰Ž—…‘•‡–‘Ž‡”ƒ…‡ƒ†‹•—Ž‹”‡•‹•–ƒ…‡ ™‹–Šƒ‰‡Ǥ

Visceral Fat, Aging and Insulin Action: Š‡ ƒ†‹’‘•‹–› ™‹–Š ƒ‰‹‰ Ž‡ƒ†• –‘ ‹…”‡ƒ•‡† ˜‹•…‡”ƒŽ ˆƒ– ȋ ȌǤ Š‡ ‡š…‡••   …‘–”‹„—–‡• –‘ ‹’ƒ‹”‡†‹•—Ž‹ƒ…–‹‘ƒ†˜ƒ”‹‘—•†‡ˆ‡…–•‹ȾǦ…‡ŽŽƒ••Ȁˆ—…–‹‘ǤŠ‡‹•—Ž‹†‡ϐ‹…‹‡…›ƒ† Ž‡ƒ†–‘‹…”‡ƒ•‡†”ƒ–‡‘ˆŽ‹’‘Ž›•‹•‹ƒ†‹’‘•‡ –‹••—‡™Š‹…Š‹…”‡ƒ•‡•…‹”…—Žƒ–‹‰ Ž‡˜‡Ž•ƒ†‡šƒ…‡”„ƒ–‡• ǡƒ†ƒ…–‹˜ƒ–‹‘‘ˆŠ‡’ƒ–‹…‰Ž—…‘‡‘‰‡‡•‹•ǡˆ—”–Š‡”ƒ††‹‰–‘Š›’‡”‰Ž›…‡‹ƒ ƒ†‹–•…‘•‡“—‡…‡•Ǥ

Conclusion-Risk Factors for Altered Glucose Homeostasis: A multitude of factors lead to the somatic carbohydrate homeostatic ƒ†‡–ƒ„‘Ž‹…‹„ƒŽƒ…‡ǤŠ‡Ž‡’–‹†‡ϐ‹…‹‡…›ƒ†”‡•‹•–ƒ…‡Ž‡ƒ†•–‘‘„‡•‹–›ƒ† ǡƒ†ƒŽ•‘ƒ••‘…‹ƒ–‡†™‹–Šƒ‰‹‰ǤŠ‡…Šƒ‰‡•‹„‘†› …‘’‘•‹–‹‘†—‡–‘†‡…”‡ƒ•‡†Ž‡ƒ„‘†›ƒ••ƒ†…‘–”ƒ…–‹Ž‡•–”‡‰–Šǡƒ†–Š‡ƒ‰‹‰Ǧƒ••‘…‹ƒ–‡†•‡†‡–ƒ”›Ž‹ˆ‡•–›Ž‡ƒ††‹‹‹•Š‡†’Š›•‹…ƒŽ ƒ…–‹˜‹–›ƒ”‡‹’‘”–ƒ–ˆƒ…–‘”•ˆ‘”ƒ‰‡Ǧ”‡Žƒ–‡†…Šƒ‰‡•‘ˆ‰Ž—…‘•‡Š‘‡‘•–ƒ•‹•Ǥ Keywords:‰‹‰Ǣ‡–ƒ„‘Ž‹…Š‘‡‘•–ƒ•‹•Ǣ •—Ž‹”‡•‹•–ƒ…‡Ǣ›’‡ʹ†‹ƒ„‡–‡•‡ŽŽ‹–—•Ǣ‡–ƒ„‘Ž‹…•›†”‘‡Ǣ ǢȾǦ…‡ŽŽ•Ǣ„‡•‹–›Ǣ†‹’‘•‹–›Ǣ ‹•…‡”ƒŽˆƒ–Ǣ‡’–‹Ǣ‹ˆ‡•–›Ž‡ˆƒ…–‘”•Ǣ‹”–—‹•ǢƒŽ‘”‹‡”‡•–”‹…–‹‘

Abbreviations: ǣ •—Ž‹ ‡•‹•–ƒ…‡Ǣ  ǣ ‹•…‡”ƒŽ ƒ–Ǣ ʹǣ ›’‡ ʹ ‹ƒ„‡–‡• ‡ŽŽ‹–—•Ǣ  ǣ Ž—…‘•‡Ǧ–‹—Žƒ–‡† •—Ž‹ ‡…”‡–‹‘Ǣ ǣ ƒ”†‹‘˜ƒ•…—Žƒ” ‹•‡ƒ•‡Ǣ ǣ ŽœŠ‡‹‡” †‹•‡ƒ•‡Ǣ ǣ Ž›…‡”‘ŽǦŠ‘•’Šƒ–‡ ‡Š›†”‘‰‡ƒ•‡Ǣ ǣ ƒ”‰‡ ‡•‡ ‘”‡ ‡•‹…Ž‡•Ǣ ǣ •Ž‡– ›Ž‘‹†‘Ž›’‡’–‹†‡ǢǣƒŽ‘”‹‡‡•–”‹…–‹‘Ǣǣ†‘’Žƒ•‹…‡–‹…—Ž—Ǣ ǣ‡’ƒ–‹… Ž—…‘•‡”‘†—…–‹‘ǢǣƒŽ‘”‹‡‡•–”‹…–‹‘‹–Š †‡“—ƒ–‡—–”‹–‹‘ǢǦǣ‹…‘–‹ƒ‹†‡†‡‹‡‹—…Ž‡‘–‹†‡Ǧ

Introduction Homeostasis and Metabolism Homeostasis refers to the body’s ability to physiologically regulate its inner milieu and ensure its stability in response –‘ ϐŽ—…–—ƒ–‹‘• ‹ –Š‡ ‘—–•‹†‡ ‡˜‹”‘‡–Ǥ Š‡”‡ ‹• ƒ …Ž‘•‡ ”‡Žƒ–‹‘•Š‹’„‡–™‡‡Š‘‡‘•–ƒ•‹•ƒ†‡–ƒ„‘Ž‹•Ǥ‘’–‹ƒŽ ‡–ƒ„‘Ž‹…‡ˆϐ‹…‹‡…›‹•ƒ‹–ƒ‹‡†„›–Š‡‡‰ƒ–‹˜‡ˆ‡‡†„ƒ…Ž‘‘’• by which homeostasis operates, and in event of any disruption ‹ Š‘‡‘•–ƒ•‹•ǡ ‡–ƒ„‘Ž‹• ™‹ŽŽ „‡ ‡‰ƒ–‹˜‡Ž› ƒˆˆ‡…–‡†Ǥ Š‡ inability to maintain homeostasis leads homeostatic imbalance, OAJ Gerontol & Geriatric Med 3(2): OAJGGM.MS.ID.555607 (2018)

resulting in various disorders and disease states including †‹ƒ„‡–‡•Ǥ

Metabolic Alterations with Aging

Š‡ ƒ‰‹‰ ‹• …ƒ „‡ †‡ϐ‹‡† ƒ• –Š‡ ƒ……——Žƒ–‹‘ ‘ˆ alterations over time at cellular, tissue and organ level in an ‘”‰ƒ‹•Ǥ––Š‡…‡ŽŽ—Žƒ”Ž‡˜‡Ž•—…Š…Šƒ‰‡•‡–ƒ‹Ž…‡••ƒ–‹‘‘ˆ DNA replication and cell division; the cells become senescent ƒ†—†‡”‰‘ƒ’‘’–‘•‹•Ǥ —”–Š‡”ǡ–Š‡ƒ‰‹‰…‡ŽŽ•ƒ”‡…Šƒ”ƒ…–‡”‹œ‡† by alterations in the rate and accuracy of protein synthesis as 001

Open Access Journal of Gerontology & Geriatric Medicine …‘’ƒ”‡†–‘›‘—‰‘‡•ȏͳȐǤŠ‡ƒ‰‹‰ƒŽ•‘ƒˆˆ‡…–•…ƒ”„‘Š›†”ƒ–‡ Š‘‡‘•–ƒ•‹•„›ƒŽ–‡”‹‰’ƒ…”‡ƒ–‹…Ⱦ…‡ŽŽˆ—…–‹‘ǡȾ…‡ŽŽƒ••ǡ insulin secretion and insulin sensitivity, and predisposes for ‹•—Ž‹”‡•‹•–ƒ…‡ȋ Ȍǡ‹’ƒ‹”‡†‰Ž—…‘•‡–‘Ž‡”ƒ…‡ƒ††‹ƒ„‡–‡•Ǥ

Aging is an important risk factor for metabolic disorders including obesity, impaired glucose tolerance, and type 2 diabetes ‡ŽŽ‹–—• ȋʹȌǤ Š‡ ’”‡˜ƒŽ‡…‡ ‘ˆ ʹ ‹…”‡ƒ•‡• ™‹–Š ƒ‰‡ ƒ† ’‡ƒ• ƒ– ͸ͲǦ͹Ͷ ƒ† †‹ƒ„‡–‡• ƒ† ‹–• …‘’Ž‹…ƒ–‹‘• ƒ”‡ ƒ ƒŒ‘” …ƒ—•‡ ‘ˆ ‘”„‹†‹–› ƒ† ‘”–ƒŽ‹–› ™‘”Ž†Ǧ™‹†‡ ȏʹȐǤ „‘—– one third of the elderly have diabetes and three quarters have †‹ƒ„‡–‡•‘”’”‡†‹ƒ„‡–‡•ǤŠ‡†‹ƒ„‡–‡•‹‹–•‡Žˆ‹…”‡ƒ•‡•–Š‡”‹• ˆ‘”—Ž–‹’Ž‡‘–Š‡”ƒ‰‡Ǧ”‡Žƒ–‡††‹•‡ƒ•‡••—…Šƒ•ƒ–Š‡”‘•…Ž‡”‘•‹•ǡ …ƒ”†‹‘˜ƒ•…—Žƒ” †‹•‡ƒ•‡ ȋȌǡ •–”‘‡ǡ ŽœŠ‡‹‡” †‹•‡ƒ•‡ ȋȌǡ ƒ”‹•‘ǯ•†‹•‡ƒ•‡ƒ†…ƒ…‡”ȏ͵ȐǤŠ‡•ƒŽ‹‡–ˆ‡ƒ–—”‡•‘ˆʹ with aging are peripheral insulin resistance and impaired insulin •‡…”‡–‹‘ˆ”‘Ⱦ…‡ŽŽ•ȏͶȐǤŠ‡ƒ‰‹‰’”‡†‹•’‘•‡•–‘†‹ƒ„‡–‡•ƒ† impaired glucose tolerance through effects on insulin secretion ƒ†‹•—Ž‹ƒ…–‹‘Ǥ

Physiology of Insulin Secretion and Aging

Insulin is the major hormone for regulating glucose Š‘‡‘•–ƒ•‹•Ǥ –„‹†•–‘‹–•”‡…‡’–‘”•Ž‘…ƒ–‡†‘˜ƒ”‹‘—•–‹••—‡• including muscle, liver, and adipose tissue and initiates signalling ‡ˆˆ‡…–•Ǥ Š‡ ‡–ƒ„‘Ž‹… ‡ˆˆ‡…–• ”‡•—Ž–‹‰ ˆ”‘ ‹•—Ž‹ •‹‰ƒŽŽ‹‰ include regulation of glucose homeostasis through a decrease ‹ Š‡’ƒ–‹… ‰Ž—…‘•‡ ‘—–’—– ȋ˜‹ƒ †‡…”‡ƒ•‡† ‰Ž—…‘‡‘‰‡‡•‹• ƒ† ‰Ž›…‘‰‡‘Ž›•‹•Ȍ ƒ† ‹…”‡ƒ•‡ ‹ ‰Ž—…‘•‡ —’–ƒ‡ ’”‹ƒ”‹Ž› ‹–‘ striated muscle and adipose tissue, and increase in lipid synthesis and attenuation of release of free fatty acid from triglycerides ˆ”‘ƒ†‹’‘•‡–‹••—‡Ǥ •—Ž‹•‡…”‡–‹‘ˆ”‘Ⱦ…‡ŽŽ•‹•ƒ…‘’Ž‡š process and involves the integration of various stimuli, such as nutrients mainly glucose and amino acid, hormones and ‡—”‘–”ƒ•‹––‡”•ȏͷȐǤ

Aging and Glucose Metabolism Insulin Secretion and IR

Figure 1: Impact of Aging on Insulin Secretion.

‹–Š ƒ‰‡ǡ –Š‡”‡ ‹• †‡…”‡ƒ•‡† ‹•—Ž‹ •‡…”‡–‹‘ ˆ‘ŽŽ‘™‹‰ •–‹—Ž—• ȋ ‹‰—”‡ ͳȌǡ †‹•‘”†‡”Ž› ‹•—Ž‹ ”‡Ž‡ƒ•‡ǡ †‡…”‡ƒ•‡† insulin pulse amplitudes, and decreased response to glucose ‘•…‹ŽŽƒ–‹‘•ƒ•™‡ŽŽƒ•ƒŽ–‡”ƒ–‹‘•‹‹•—Ž‹…Ž‡ƒ”ƒ…‡ȏ͸ȐǤƒ› factors lead to decreased insulin secretion with age and include –Š‡ƒ‰‡Ǧƒ••‘…‹ƒ–‡†Ž‘••‘ˆ‹”–ͳǦ‡†‹ƒ–‡†  ǡ†‡…”‡ƒ•‡†ȾǦ…‡ŽŽ 002

•‡•‹–‹˜‹–› –‘ …‹”…—Žƒ–‹‰ ‹…”‡–‹•ǡ ƒ‰‡Ǧƒ••‘…‹ƒ–‡† †‡…”‡ƒ•‡ ‹ mitochondrial function, as well as increased oxidative stress ȏ͹ǡͺȐǤ •—Ž‹ ”‡•‹•–ƒ…‡ ”‡•—Ž–• ™Š‡ ‘”ƒŽ …‹”…—Žƒ–‹‰ …‘…‡–”ƒ–‹‘• ‘ˆ –Š‡ Š‘”‘‡ ƒ”‡ ‹•—ˆϐ‹…‹‡– –‘ ”‡‰—Žƒ–‡ –Š‡ ‰Ž—…‘•‡‡–ƒ„‘Ž‹…’”‘…‡••‡•ƒ’’”‘’”‹ƒ–‡Ž›Ǥ

Š‡ ‹•—Ž‹ •‡…”‡–‘”› †‡ˆ‡…–• ƒ”‡ •—’‡”‹’‘•‡† ‘ ƒ increased insulin demand because of increased insulin resistance with age results in impaired glucose homeostasis, ‰Ž—…‘•‡ ‹–‘Ž‡”ƒ…‡ ƒ† †‹ƒ„‡–‡•Ǥ —”–Š‡”ǡ ƒ‰‹‰ ‹• ƒ••‘…‹ƒ–‡† with a decline of insulin action, which contributes to the high ’”‡˜ƒŽ‡…‡‘ˆ‹’ƒ‹”‡†‰Ž—…‘•‡–‘Ž‡”ƒ…‡ƒ†ʹƒ‘‰–Š‡ ‡Ž†‡”Ž›Ǥ

Ž—…‘•‡”ƒ•’‘”–‡”•‹Ⱦ‡ŽŽ•

Š‡ ‹‹–‹ƒ–‹‘ ‘ˆ –Š‡ ‰Ž—…‘•‡ –”ƒ•’‘”– ‹• –Š‡ ϐ‹”•– •–‡’ –Šƒ– Ž‹• ‰Ž—…‘•‡ ‡–ƒ„‘Ž‹• –‘ ‹•—Ž‹ ”‡Ž‡ƒ•‡ ‹ –Š‡ Ⱦ …‡ŽŽǤ

ʹ‹•–Š‡ƒ‹–”ƒ•’‘”–‡”ǡ„—– ͳƒ† ͵ƒ”‡ƒŽ•‘ ‹’‘”–ƒ–ǤŠ‡‰Ž—…‘•‡–”ƒ•’‘”–‡”•‡š’”‡••‡†‹Ⱦ…‡ŽŽ•‡•—”‡ ƒ „‹†‹”‡…–‹‘ƒŽ ϐŽ—š ‘ˆ ‰Ž—…‘•‡ ƒ† ‘–Š‡” †‹‡–ƒ”› •—‰ƒ”•ǡ •—…Š ƒ• ˆ”—…–‘•‡ ƒ† ‰ƒŽƒ…–‘•‡Ǥ Š‡ ʹ ‹• ‡••‡–‹ƒŽ ˆ‘” ‰Ž—…‘•‡Ǧ •–‹—Žƒ–‡† ‹•—Ž‹ •‡…”‡–‹‘ ȋ  Ȍ ƒ† †‡ϐ‹…‹‡…› ‘ˆ ʹ …ƒ—•‡• Š›’‡”‰Ž›…‡‹ƒ ȏͻȐǤ Š‡ Ž‘•• ‘ˆ ’ƒ…”‡ƒ–‹… ȾǦ…‡ŽŽ ʹ expression is, thus, associated with hyperglycemia and impaired

  ȏͳͲȐǤ Š‡ ƒ‰‡Ǧƒ••‘…‹ƒ–‡† †‡…”‡ƒ•‡ ‹ ʹ ‡š’”‡••‹‘ Šƒ• „‡‡ †‘…—‡–‡† ‹ ƒ‰‡† ”‘†‡– ‘†‡Ž• ȏͳͳȐǤ Š‡ Š—ƒ Ⱦ…‡ŽŽ•ǡƒ•…‘’ƒ”‡†–‘”‘†‡–•Ⱦ…‡ŽŽ•ǡ‡š’”‡••ƒŽŽ–Š”‡‡‰Ž—…‘•‡ –”ƒ•’‘”–‡”•ǡ ͳǡ ʹǡ ƒ† ͵ǡ ƒ† –Š‡ Ž‡˜‡Ž• ‘ˆ ͳ ƒ†

͵ƒ”‡ƒŽ•‘‹’‘”–ƒ–ƒ’ƒ”–ˆ”‘ ʹ‹‹Š—ƒ•ȏͳʹȐǤ

‰‹‰ƒ†ȾǦ‡ŽŽ Ž—…‘•‡š‹†ƒ–‹‘

ˆ–‡”–”ƒ•’‘”–‹–‘–Š‡Ⱦ…‡ŽŽ•ǡ‰Ž—…‘•‡—†‡”‰‘‡•‘š‹†ƒ–‹‘ǡ ‹‹–‹ƒ–‡† „› ‹–• ’Š‘•’Š‘”›Žƒ–‹‘ „› ‰Ž—…‘‹ƒ•‡ ȋ Ȍǡ ƒ Š‡š‘‹ƒ•‡ǡƒ†‰‡‡”ƒ–‡•‹…›–‘•‘Žƒ†‹–‘…Š‘†”‹ƒ˜‹ƒ –Š‡ –”‹…ƒ”„‘š›Ž‹… ƒ…‹† ȋȌ …›…Ž‡ǡ ”‡•—Ž–‹‰ ‹ „—‹Ž†Ǧ—’ ‹ –Š‡ ™Š‹…Š‹•”‡“—‹”‡†ˆ‘”‹•—Ž‹•‡…”‡–‹‘ǤŠ‡‡–ƒ„‘Ž‹•‘ˆ ‰Ž—…‘•‡‹Ⱦ…‡ŽŽ•ˆ”‘ʹ’ƒ–‹‡–•‡šŠ‹„‹–Ž‘™‡”…‘–‡– ƒ† ƒ „Ž—–‡†  ǡ ƒ† ƒ’’‡ƒ” –‘ „‡ ”‡•’‘•‹„Ž‡ ˆ‘” Ⱦ …‡ŽŽ †›•ˆ—…–‹‘ȏͳ͵ȐǤ

  Ž‡˜‡Ž Šƒ• •Š‘™ –‘ „‡ †‡…”‡ƒ•‡† ‹ †‹ƒ„‡–‹… …‘’ƒ”‡† –‘ –Š‡ ‘”ƒŽ ”ƒ–• ƒ† –Š‡ ‰‡‡ ‡š’”‡••‹‘ ˆ‘”  ‹• •‹‰‹ϐ‹…ƒ–Ž› ‹…”‡ƒ•‡† ™‹–Š ƒ‰‡ ‹ Š‡ƒŽ–Š› ”ƒ–•ǡ •—‰‰‡•–‹‰ ƒ ’‘–‡–‹ƒŽ ‡…Šƒ‹• „› ™Š‹…Š Ⱦ …‡ŽŽ• ƒ––‡’– –‘ ‘˜‡”…‘‡ ƒ‰‡Ǧƒ••‘…‹ƒ–‡† ‰Ž—…‘•‡ ‹–‘Ž‡”ƒ…‡ ƒ† ‹•—Ž‹ ”‡•‹•–ƒ…‡ ȏͳͶȐǤ Š‡ ’ƒ…”‡ƒ–‹… ‹•Ž‡– Šƒ• ƒ„‘—– ͶͲǦ͹Ͳ –‹‡• –Š‡ ƒ…–‹˜‹–› ‘ˆ ‹–‘…Š‘†”‹ƒŽ ‰Ž›…‡”‘ŽǦ’Š‘•’Šƒ–‡ †‡Š›†”‘‰‡ƒ•‡ ȋ Ȍ …‘’ƒ”‡†–‘‘–Š‡”–‹••—‡•ǤŠ‡†‡…”‡ƒ•‡‹ ƒ…–‹˜‹–›Ž‡ƒ†• –‘†‡…”‡ƒ•‡‹‰Ž›…‘Ž›•‹•ƒ†  ǤŠ‹•Šƒ•„‡‡•—’’‘”–‡†„› animal studies, older rats showing approximately 50% reduction ‹–Š‡ ƒ…–‹˜‹–›‹‹•Ž‡–•…‘’ƒ”‡†™‹–Š›‘—‰”ƒ–•ȏͳͷȐǤ

Aging and Calcium and Potassium Channels

Š‡ ‹…”‡ƒ•‡† Ȁ ”ƒ–‹‘ ˆ‘ŽŽ‘™‹‰ ‰Ž—…‘•‡ ‘š‹†ƒ–‹‘ ”‡†—…‡•–Š‡™Š‘Ž‡…‡ŽŽ+ permeability, leads to cell membrane †‡’‘Žƒ”‹œƒ–‹‘ ƒ† ‡š–”ƒ…‡ŽŽ—Žƒ” ƒ2+ ‹ϐŽ—š ‹–‘ –Š‡ Ⱦ …‡ŽŽǤ

How to cite this article: Vinod Nikhra. The Altered Metabolic Homeostasis in Middle Aged and Elderly: Aging and Other Determinants of Insulin Secretion, Action and Resistance. OAJ Gerontol & Geriatric Med. 2018; 3(2): 555608.

Open Access Journal of Gerontology & Geriatric Medicine ‘ŽŽ‘™‹‰ƒ2+ ‹ϐŽ—šǡ–Š‡”‡‘……—”•‡Ž‡˜ƒ–‹‘‘ˆ…›–‘•‘Ž‹…ˆ”‡‡ƒ2+ …‘…‡–”ƒ–‹‘™Š‹…Š‹‹–‹ƒ–‡•–Š‡‹•—Ž‹‡š‘…›–‘•‹•ǤŠ‡ƒ‹ƒŽ studies suggest that the decreased insulin secretory response to glucose in aged rats is due, at least in part, to inadequate ‹Š‹„‹–‹‘‘ˆΪ‡ˆϐŽ—šƒ††‹‹‹•Š‡†‡–ƒ2+ —’–ƒ‡ȏͳ͸ȐǤ

ˆˆ‡…–•‘ˆ‰‡‘ •—Ž‹ ”ƒ—Ž‡š‘…›–‘•‹•

Š‡ ϐ‹ƒŽ •–‡’ ‘ˆ ‹•—Ž‹ •‡…”‡–‹‘ ‹• –Š‡ ‡š‘…›–‘•‹• ‘ˆ ‹•—Ž‹ ‰”ƒ—Ž‡•Ǥ •—Ž‹ ‹• •–‘”‡† ‹ Žƒ”‰‡ †‡•‡ …‘”‡ ˜‡•‹…Ž‡• ȋ•ȌǡƒŽ•‘…ƒŽŽ‡†‹•—Ž‹‰”ƒ—Ž‡ǡƒ†”‡Ž‡ƒ•‡†„›‡š‘…›–‘•‹•ǡ ƒ —Ž–‹•–ƒ‰‡ ’”‘…‡•• ‹˜‘Ž˜‹‰ ˜‡•‹…Ž‡ –”ƒˆϐ‹…‹‰ǡ †‘…‹‰ǡ ƒ† ‡˜‡–—ƒŽŽ› ˆ—•‹‘ ™‹–Š –Š‡ ’Žƒ•ƒ ‡„”ƒ‡Ǥ ƒŽ…‹— constitutes the major stimulus for exocytosis and regulates •‡˜‡”ƒŽ•–‡’•‹‡š‘…›–‘•‹•ǡ•—…Šƒ•–Š‡•‹œ‡‘ˆ˜‡•‹…Ž‡’‘‘Ž•ǡ–Š‡ ˆ—•‹‘ ‡˜‡–ǡ ƒ† –Š‡ •‹œ‡ ‘ˆ –Š‡ ˆ—•‹‘ ’‘”‡ǡ ƒ† ƒ› ƒ…– ‘ †‹•–‹…–’”‘–‡‹–ƒ”‰‡–•Ǥ‹…‡–Š‡‡–—’–ƒ‡‘ˆƒ2+ is decreased with age, it is reasonable to speculate that insulin granule ‡š‘…›–‘•‹•‹•ƒŽ•‘‹Š‹„‹–‡†„›ƒ‰‡Ǥ

‰‹‰ƒ†ȾǦ‡ŽŽƒ••ƒ†‹•…‡”ƒŽ ƒ– Š‡ȾǦ…‡ŽŽƒ••—”‘˜‡”

Š‡ ‹•Ž‡–• ȾǦ…‡ŽŽ ƒ•• ‹• ”‡‰—Žƒ–‡† „› –Š‡ „ƒŽƒ…‡ ‘ˆ …‡ŽŽ ’”‘Ž‹ˆ‡”ƒ–‹‘ƒ†ƒ’‘’–‘•‹•ǤŠ‡ȾǦ…‡ŽŽƒ••‘”ƒŽŽ›‰”‘™•™‡ŽŽ into adulthood to provide increased insulin secretion to match –Š‡ ‰”‡ƒ–‡” ‹•—Ž‹ ”‡“—‹”‡‡–• ™‹–Š ‰”‘™–ŠǤ Š‡ ȾǦ…‡ŽŽ ƒ•• Šƒ•ƒŽ•‘„‡‡•Š‘™–‘‡š’ƒ†‹ƒ†—Ž–”‘†‡–•†—”‹‰’”‡‰ƒ…›Ǥ Š‡”‡ƒˆ–‡”ǡ–Š‡”ƒ–‡‘ˆȾǦ…‡ŽŽ’”‘Ž‹ˆ‡”ƒ–‹‘‰”ƒ†—ƒŽŽ›†‡…Ž‹‡•™‹–Š ƒ‰‹‰ ȋ ‹‰—”‡ ʹȌǤ  ƒ††‹–‹‘ǡ –Š‡ ›‘—‰ ‹…‡ ”‡•’‘† –‘ Š‹‰ŠǦ ˆƒ– †‹‡– „› ‹…”‡ƒ•‹‰ ȾǦ…‡ŽŽ ƒ•• „› ’”‘Ž‹ˆ‡”ƒ–‹‘ –‘ ƒ‹–ƒ‹ ‘”ƒŽ„Ž‘‘†‰Ž—…‘•‡Ž‡˜‡Ž•ǤŠ‡‘Ž†‡”‹…‡ǡ‹…‘–”ƒ•–ǡ†‘‘– †‹•’Žƒ›‹…”‡ƒ•‡‹ȾǦ…‡ŽŽƒ••‘”ȾǦ…‡ŽŽ’”‘Ž‹ˆ‡”ƒ–‹‘‹”‡•’‘•‡ –‘Š‹‰ŠǦˆƒ–†‹‡–ƒ†„‡…‘‡†‹ƒ„‡–‹…Ǥ —”–Š‡”ǡ˜ƒ”‹‘—•ƒ•’‡…–•‘ˆ ȾǦ…‡ŽŽƒ••ƒ†ˆ—…–‹‘†‡…Ž‹‡™‹–Šƒ‰‡ǡ–Š—•…‘–”‹„—–‹‰–‘ –Š‡ƒ‰‡Ǧƒ••‘…‹ƒ–‡††‡ˆ‡…–•‹‹•—Ž‹•‡…”‡–‹‘ǤŠ‹•†‡ˆ‡…–™Š‡ superimposed on an increased demand for insulin, contributes to ‹’ƒ‹”‡†‰Ž—…‘•‡Š‘‡‘•–ƒ•‹•ǡ‰Ž—…‘•‡‹–‘Ž‡”ƒ…‡ƒ††‹ƒ„‡–‡•Ǥ

Figure 2: ,PSDFWRIDJLQJRQȕFHOO0DVVDQG9)

In fact, the age correlates with a decreased proliferative ƒ…–‹˜‹–› ƒ† ƒ ‡Šƒ…‡† •‡•‹–‹˜‹–› –‘ ‰Ž—…‘•‡Ǧ‹†—…‡† ȾǦ…‡ŽŽ ƒ’‘’–‘•‹•ȏͳ͹ȐǤŠ‡”‡‹•ƒ‹…”‡ƒ•‡†ȾǦ…‡ŽŽƒ’‘’–‘•‹•‹†‹ƒ„‡–‹… ’ƒ–‹‡–•ǡ ˜ƒ”›‹‰ ˆ”‘ ͵ǦͳͲ ˆ‘Ž†•ǡ ƒ• …‘’ƒ”‡† –‘ ‘†‹ƒ„‡–‹… ‹†‹˜‹†—ƒŽ• ȏͳͺȐǤ Š‡ Š‹‰Š ‰Ž—…‘•‡ Ž‡˜‡Ž ‹†—…‡• ƒ’‘’–‘•‹• ‹ Ⱦ 003

…‡ŽŽ• –Š”‘—‰Š ‹†—…‹‰ –Š‡ ‡š’”‡••‹‘ ‘ˆ ƒ• ƒ† ƒ…–‹˜ƒ–‹‘ ‘ˆ …ƒ•’ƒ•‡ ͺ ƒ† ͵ ȏͳͻȐǤ ‹—Ž–ƒ‡‘—•Ž›ǡ –Š‡”‡ ‹• ƒ‰‡Ǧƒ••‘…‹ƒ–‡† †‡…”‡ƒ•‡ ‹ ƒ…–‹˜‹–‹‡• ‘ˆ ˜ƒ”‹‘—• ƒ–‹‘š‹†ƒ– ‡œ›‡• ƒ† ƒ ‹…”‡ƒ•‡†‘š‹†ƒ–‹˜‡•–”‡••™Š‹…Š…‘–”‹„—–‡•–‘‹…”‡ƒ•‡†Ⱦ…‡ŽŽ• ƒ’‘’–‘•‹•Ǥ ‡‡”• ‡– ƒŽǡ ‘ –Š‡ ‘–Š‡” Šƒ†ǡ Šƒ˜‡ ”‡’‘”–‡† –Šƒ– –Š‡ ”‡Žƒ–‹˜‡ ȾǦ…‡ŽŽ ˜‘Ž—‡ ‹ Š—ƒ ’ƒ…”‡ƒ–‹… ‹•Ž‡–• ”‡ƒ‹• …‘•–ƒ– ™‹–Š ƒ‰‹‰ ƒ† ȾǦ…‡ŽŽ ƒ’‘’–‘•‹• †‘‡• ‘– ‹’ƒ…– •‹‰‹ϐ‹…ƒ–Ž›ǡ„—––Š‡ȾǦ…‡ŽŽ”‡’Ž‹…ƒ–‹‘†‡…”‡ƒ•‡•™‹–Šƒ‰‡ȏʹͲȐǤ

›Ž‹ ‘” ‹•Ž‡– ƒ›Ž‘‹† ’‘Ž›’‡’–‹†‡ ȋ Ȍ ‹• ƒŽ•‘ …‘Ǧ •‡…”‡–‡†ƒŽ‘‰™‹–Š‹•—Ž‹ˆ”‘Ⱦ…‡ŽŽ•Ǥ›Ž‹•—’’”‡••‡•–Š‡ ‰Ž—…ƒ‰‘•‡…”‡–‹‘ƒ†Š‡Ž’•–‘”‡‰—Žƒ–‡‰Ž—…‘•‡Š‘‡‘•–ƒ•‹•Ǥ  ‹•—Ž‹Ǧ”‡•‹•–ƒ–•–ƒ–‡•ǡ–Š‡‹…”‡ƒ•‡†•‡…”‡–‹‘‘ˆ‹•—Ž‹”‡•—Ž–• ‹ Š›’‡”•‡…”‡–‹‘ ‘ˆ ƒ›Ž‹Ǥ ‹–Š ƒ‰‡ –Š‡”‡ ‹• ƒ ‹…”‡ƒ•‡† deposition of amylin in the islets of diabetic patients, which ƒ‰‰”‡‰ƒ–‡• ‹–‘ ƒ›Ž‘‹† ’Žƒ“—‡• –Šƒ– ‹†—…‡ ȾǦ…‡ŽŽ ƒ’‘’–‘•‹• Ž‡ƒ†‹‰–‘”‡†—…‡†‹•Ž‡–˜‘Ž—‡ƒ†ȾǦ…‡ŽŽƒ••ȏʹͳȐǤ

Š‡ ‹•Ž‡– ‡‘‰‡‡•‹• ‹• –Š‡ †‹ˆˆ‡”‡–‹ƒ–‹‘ ‘ˆ ’”‘‰‡‹–‘” …‡ŽŽ ‘” –”ƒ•Ǧ†‹ˆˆ‡”‡–‹ƒ–‹‘ ‘ˆ ’ƒ…”‡ƒ–‹… ‘ǦȾ …‡ŽŽ• –‘ Ⱦ …‡ŽŽ•Ǥ ‡‘‰‡‡•‹• ‘ˆ ‹•Ž‡–• ‘……—”• †—”‹‰ ‘”ƒŽ ‡„”›‘‹… †‡˜‡Ž‘’‡– ƒ† ‡ƒ”Ž› ’‘•–ƒ–ƒŽ Ž‹ˆ‡ Ž‡ƒ†‹‰ –‘ ȾǦ…‡ŽŽ ƒ•• ‡š’ƒ•‹‘Ǥ ƒ††‹–‹‘ǡȾ…‡ŽŽ‡‘‰‡‡•‹•Šƒ•„‡‡•Š‘™–‘‘……—” in the adults during periods of increased insulin demand such ƒ• ’”‡‰ƒ…› ƒ† ‘„‡•‹–›Ǥ Š‡ ’‘–‡–‹ƒŽ ˆ‘” ȾǦ…‡ŽŽ ”‡’Ž‹…ƒ–‹‘ †‡…Ž‹‡• •‹‰‹ϐ‹…ƒ–Ž› ™‹–Š ƒ‰‡ǡ „—– –Š‡ ”ƒ–‡ ‘ˆ ‹•Ž‡– ‡‘‰‡‡•‹• ȋ‡š’”‡••‡†ƒ•’‡”…‡–ƒ‰‡‘ˆ‹•—Ž‹’‘•‹–‹˜‡†—…–…‡ŽŽ•Ȍ†‘‡•‘– ƒ’’‡ƒ”–‘„‡ƒˆˆ‡…–‡†„›ƒ‰‹‰‹Š—ƒ•Ǥ

Visceral Fat, Aging and Insulin Action

Š‡ ˜‹•…‡”ƒŽ ˆƒ– ȋ Ȍ Ž‘…ƒ–‡† ‹ ƒ† ƒ”‘—† –Š‡ ƒ„†‘‹ƒŽ ˜‹•…‡”ƒǡƒ†‡š…‡•• Šƒ•„‡‡”‡Žƒ–‡†–‘˜ƒ”‹‘—•’ƒ–Š‘Ž‘‰‹…ƒŽ •–ƒ–‡• ‹…Ž—†‹‰ ‡–ƒ„‘Ž‹… •›†”‘‡ ƒ† ǡ  ƒ† ʹ ȏʹʹȐǤ Š‡   Šƒ• „‡‡ ”‡Žƒ–‡† –‘ ƒ‰‹‰ǡ ƒ† ƒ• †‡–‡”‹ƒ– ‘ˆ ‹•—Ž‹ ƒ…–‹‘ ȏʹ͵ȐǤ Š‡ ƒ†‹’‘•‹–› ™‹–Š ƒ‰‹‰ ƒ’’‡ƒ”• –‘ „‡ ƒ ‹’‘”–ƒ–ƒ••‘…‹ƒ–‹‘ȏʹͶȐǤ ˆƒ…–ǡ–Š‡ ‹…”‡ƒ•‡•–Š”‘—‰Š‘—– the lifespan in men and women of all ages and race, independent ‘ˆ ‹…”‡ƒ•‡• ‹ „‘†› ™‡‹‰Š– ȏʹͷȐǤ ƒ”‹‘—• ˆƒ…–‘”• …‘–”‹„—–‡ –‘ –Š‡ ‹…”‡ƒ•‡†   •‡‡ ™‹–Š ƒ‰‹‰ •—…Š ƒ• ’Š›•‹‘Ž‘‰‹… †‡…Ž‹‡ ‹ Ȁ Ǧͳƒš‹•ǡ†‡…”‡ƒ•‡‹•‡š•–‡”‘‹†•ƒ•™‡ŽŽƒ••‡†‡–ƒ”› Ž‹ˆ‡•–›Ž‡ǤŠ‡”‡‘˜ƒŽ‘ˆ ’”‡˜‡–•–Š‡’”‘‰”‡••‹˜‡†‡…Ž‹‡‹ ‹•—Ž‹ƒ…–‹‘ƒ†‹’”‘˜‡•‘”†‡Žƒ›•–Š‡‘•‡–‘ˆ†‹ƒ„‡–‡•ȏʹ͸ȐǤ ƒŽ‘”‹‡”‡•–”‹…–‹‘ȋȌ‡š–‡†•Ž‹ˆ‡•’ƒƒ†”‡–ƒ”†•ƒ‰‡Ǧ”‡Žƒ–‡† …Š”‘‹…†‹•‡ƒ•‡•‹ƒ˜ƒ”‹‡–›‘ˆ•’‡…‹‡•ǡ‹…Ž—†‹‰ƒ……Šƒ”‘›…‡•ǡ ‡Ž‡‰ƒ•ǡ”‘•‘’Š‹Žƒǡ”‘†‡–•ƒ†”Š‡•—•‘‡›•ȏʹ͹ȐǤƒ”‹‘—• •–—†‹‡• Šƒ˜‡ •Š‘™ –Šƒ– –Š‡ ”‡†—…–‹‘ ‹ ˆƒ– ƒ••ǡ •’‡…‹ϐ‹…ƒŽŽ›  ǡ ƒ› „‡ ‘‡ ‘ˆ –Š‡ ’‘••‹„Ž‡ —†‡”Ž›‹‰ ‡…Šƒ‹•• ‘ˆ –Š‡ ƒ–‹ƒ‰‹‰‡ˆˆ‡…–‘ˆȏʹͺȐǤ

Š‡ ƒ†‹’‘•‡ –‹••—‡ ‹• ƒ ƒ…–‹˜‡ ‡–ƒ„‘Ž‹…Ǧ‡†‘…”‹‡ ‘”‰ƒ ȏʹͻȐǤ Š‡ ‘„‡•‹–› ‹• ƒ Ž‘™Ǧ‰”ƒ†‡ ‹ϐŽƒƒ–‘”› …‘†‹–‹‘ ƒ† Šƒ• „‡‡ ”‡Žƒ–‡† –‘ ƒ†˜‡”•‡ ‡–ƒ„‘Ž‹… ‘—–…‘‡ ȏ͵ͲȐǤ —”–Š‡”ǡ –Š‡ ƒ†‹’‘•‹–› ‹…”‡ƒ•‡• ™‹–Š ƒ‰‡ ƒ† ‹…”‡ƒ•‡†   ‹†—…‡• ‹ϐŽƒƒ–‘”› •–ƒ–‡ǡ ™Š‹…Š ‹…”‡ƒ•‡• –Š‡ ”‹• ‘ˆ ǡ ‰Ž—…‘•‡ ‹–‘Ž‡”ƒ…‡ǡ ʹǡ ǡ ƒ† Š›’‡”–‡•‹‘ǡ ƒ† ƒ……‡Ž‡”ƒ–‡•

How to cite this article: Vinod Nikhra. The Altered Metabolic Homeostasis in Middle Aged and Elderly: Aging and Other Determinants of Insulin Secretion, Action and Resistance. OAJ Gerontol & Geriatric Med. 2018; 3(2): 555608.

Open Access Journal of Gerontology & Geriatric Medicine –Š‡ ’”‘…‡•• ‘ˆ ƒ‰‹‰Ǥ  ƒ†Ȁ‘” ‹•—Ž‹ †‡ϐ‹…‹‡…› Ž‡ƒ† –‘ –™‘ metabolic alterations, namely, increased rate of lipolysis in ƒ†‹’‘•‡ –‹••—‡ ™Š‹…Š ‹…”‡ƒ•‡• …‹”…—Žƒ–‹‰  Ž‡˜‡Ž• ƒ† exacerbates IR, and activation of hepatic gluconeogenesis in •’‹–‡ ‘ˆ Š‹‰Š ’Žƒ•ƒ ‰Ž—…‘•‡ Ž‡˜‡Ž•Ǥ Š‡ ‡Ž‡˜ƒ–‡† ’Žƒ•ƒ  ‡šƒ…‡”„ƒ–‡• ȏ͵ͳȐǤŠ‡‡Ž‡˜ƒ–‡†Ž‡˜‡Ž•‘ˆ †‡…”‡ƒ•‡‰Ž—…‘•‡ —’–ƒ‡ƒ†‰Ž›…‘‰‡•›–Š‡•‹•‹Š—ƒǡƒ†‹Š‹„‹– ͵‹ƒ•‡ ƒ…–‹˜‹–› ‹ •‡Ž‡–ƒŽ —•…Ž‡ „› ‹’ƒ‹”‡– ‘ˆ ‹•—Ž‹ •‹‰ƒŽŽ‹‰Ǥ  ƒ‹ƒŽ ‘†‡Ž•ǡ –Š‡ …‹”…—Žƒ–‹‰  Ž‡˜‡Ž• ƒ”‡ •‹‰‹ϐ‹…ƒ– Š‹‰Š‡” ‹ ‘Ž†‡” ”ƒ–• ƒ• …‘’ƒ”‡† –‘ ›‘—‰‡” ‘‡•Ǥ Š‡ Š‹‰Š Ž‡˜‡Ž•ǡ–Š—•ǡƒ›„‡–Š‡—‹ˆ›‹‰‡…Šƒ‹•–Šƒ–ƒ……‘—–• ˆ‘”–Š‡‹•—Ž‹”‡•‹•–ƒ…‡‹‘„‡•‹–›ƒ†ʹǡƒ†™‹–Šƒ‰‹‰ ȏ͵ʹȐǤŠ‡‹…”‡ƒ•‡† ƒ†Š‹‰Š…‹”…—Žƒ–‹‰ „‘–Š…‘–”‹„—–‡ –‘ ‹’ƒ‹”‡† ‹•—Ž‹ ƒ…–‹‘ ƒ† ˜ƒ”‹‘—• †‡ˆ‡…–• ‹ ȾǦ…‡ŽŽ ƒ••Ȁ ˆ—…–‹‘Ǥ

The Concept Central Insulin Resistance

Š‡ ”‡…‡– •–—†‹‡• •—‰‰‡•– –Šƒ–  ‡š‹•–• ‹  ƒ† central insulin action plays an important role in regulating •‘ƒ–‹… ‰Ž—…‘•‡ ‡–ƒ„‘Ž‹• ȏ͵͵ȐǤ  Š‡ Š›’‘–ŠƒŽƒ‹… ‹•—Ž‹ signaling is an important determinant of the response to ‹•—Ž‹ ‹ –Š‡ ƒƒ‰‡‡– ‘ˆ —…‘–”‘ŽŽ‡† †‹ƒ„‡–‡• ȏ͵ͶȐǤ Interestingly, evidence from recent research documents a link between diabetes and AD, a neurodegenerative disorder and –Š‡ …‘‘‡•– ˆ‘” ‘ˆ †‡‡–‹ƒ ȏ͵ͷȐǤ —”–Š‡”ǡ –Š‡ ’ƒ–‹‡–• ™‹–Š ʹ Šƒ˜‡ ‹…”‡ƒ•‡† ’”‡˜ƒŽ‡…‡ ‘ˆ  „› ʹǦ͵ ˆ‘Ž†•ǡ ƒ† insulin levels and insulin activity in the central nervous system ƒ”‡ ”‡†—…‡† ‹  ȏ͵͸ȐǤ Š‹• ‹• ‡†‘”•‡† „› ˜ƒ”‹‘—• •–—†‹‡• ‹ human subjects showing that administration of insulin improves ‡‘”›‹’ƒ–‹‡–•ȏ͵͹ȐǤ Š‹• „”‹‰• ƒ ‹–‡”‡•–‹‰ …‘…‡’– –Šƒ– ƒ‰‹‰ ‹• ƒ••‘…‹ƒ–‡† ™‹–Š…‡–”ƒŽ‹•—Ž‹”‡•‹•–ƒ…‡ȏ͵ͺȐǤ –Š‹•…‘–‡š–ǡ‹–Šƒ•„‡‡ shown that the protein levels of elements in the insulin signalling ’ƒ–Š™ƒ› •—…Š ƒ• • ƒ†  Š‘‘Ž‘‰› ƒ†ƒ’–‘” ’”‘–‡‹ ȋȌ †‘‘–˜ƒ”›•‹‰‹ϐ‹…ƒ–Ž›‹–Š‡ˆ‘”‡„”ƒ‹…‘”–‡šƒ†…‡”‡„‡ŽŽ— ‘ˆ‘Ž†‡”ƒ†›‘—‰”ƒ–•ȏ͵ͻȐǤŠ—•ǡ–Š‡ƒ‰‹‰Ǧƒ••‘…‹ƒ–‡†‹…”‡ƒ•‡ in central and peripheral insulin resistance could contribute to „‘–Š†‹ƒ„‡–‡•ƒ†Ǥ

Aging and Whole Body Glucose Homeostasis Impaired Glucose Tolerance

Š‡ ”‹• ˆ‘” ‹’ƒ‹”‡† ‰Ž—…‘•‡ –‘Ž‡”ƒ…‡ ƒ† †‹ƒ„‡–‡• ‹…”‡ƒ•‡™‹–Šƒ‰‡ǤŠ‡”‡ƒ”‡˜ƒ”‹‘—•ˆƒ…–‘”•™Š‹…Š’Žƒ›”‘Ž‡‹ •‘ƒ–‹…‰Ž—…‘•‡Š‘‡‘•–ƒ•‹•Ǥ‡’–‹ǡƒŠ‘”‘‡•‡…”‡–‡†ˆ”‘ ƒ†‹’‘•‡–‹••—‡ǡ’Žƒ›•ƒ‡›”‘Ž‡‹‡‡”‰›‹–ƒ‡ƒ†‡š’‡†‹–—”‡Ǥ ‡ϐ‹…‹‡…›‘ˆŽ‡’–‹ƒ†‹–•”‡…‡’–‘”Ž‡ƒ†•–‘•‡˜‡”‡‘„‡•‹–›ǡ ǡ ƒ† †‹ƒ„‡–‡• ‹ ”‘†‡–• ƒ† Š—ƒ•Ǥ ‡•‹•–ƒ– –‘ –Š‡ ‡ˆˆ‡…–• ‘ˆ Ž‡’–‹ǡ –‡”‡† Ž‡’–‹ ”‡•‹•–ƒ…‡ǡ ‹• •‡‡ ‹ ‘„‡•‹–›Ǥ ‡’–‹ ”‡•‹•–ƒ…‡ ‹• ƒŽ•‘ ƒ••‘…‹ƒ–‡† ™‹–Š ƒ‰‹‰ ȏͶͲȐǤ Š‡ ‡†‘’Žƒ•‹… ”‡–‹…—Ž—ȋȌ•–”‡••’Žƒ›•ƒ”‘Ž‡‹–Š‡’ƒ–Š‘‰‡‡•‹•‘ˆ†‹ƒ„‡–‡• „› …‘–”‹„—–‹‰ –‘ „‘–Š ’ƒ…”‡ƒ–‹… ȾǦ…‡ŽŽ †›•ˆ—…–‹‘ ƒ† ’‡”‹’Š‡”ƒŽ‹•—Ž‹”‡•‹•–ƒ…‡ȏͶͳȐǤ 004

Š‘Ž‡ „‘†› ‰Ž—…‘•‡ Š‘‡‘•–ƒ•‹• ‹• ƒ …‘’Ž‡š „ƒŽƒ…‡ ‘ˆ ‰Ž—…‘•‡ ’”‘†—…–‹‘ ƒ† —–‹Ž‹œƒ–‹‘ „› †‹ˆˆ‡”‡– –‹••—‡•Ǥ ‘‘† ‹–ƒ‡ ƒ† Š‡’ƒ–‹… ‰Ž—…‘•‡ ’”‘†—…–‹‘ ȋ Ȍ ƒ”‡ –Š‡ –™‘ sources of glucose production, while skeletal muscle contributes –‘ –Š‡ ƒŒ‘”‹–› ‘ˆ –Š‡ ‰Ž—…‘•‡ —’–ƒ‡ ƒ† —–‹Ž‹œƒ–‹‘Ǥ   plays crucial roles in glucose homeostasis, both in the fasting ƒ† ’‘•–’”ƒ†‹ƒŽ •–ƒ–‡•Ǥ Š‡ Š‡’ƒ–‹… ‰Ž—…‘•‡ ’”‘†—…–‹‘ †‘‡• ‘– ‹…”‡ƒ•‡ ™‹–Š ƒ‰‡ǡ ™Š‡ ƒ†Œ—•–‡† ˆ‘” Ž‡ƒ „‘†› ƒ•• ȏͶʹȐǤ —”–Š‡”‘”‡ǡŠ‡’ƒ–‹…‰Ž—…‘•‡‘—–’—–Šƒ•‘–„‡‡•Š‘™–‘„‡ ‹…”‡ƒ•‡† ‹ ‡Ž†‡”Ž› ’ƒ–‹‡–• ™‹–Š ʹǤ Š—•ǡ Š‡’ƒ–‹… ‹•—Ž‹ ”‡•‹•–ƒ…‡ †‘‡• ‘– •‡‡ ’Žƒ› ƒ •‹‰‹ϐ‹…ƒ– ”‘Ž‡ ‹ †‡…”‡ƒ•‡† ‰Ž—…‘•‡–‘Ž‡”ƒ…‡‘ˆ‡Ž†‡”Ž›’‡‘’Ž‡Ǥ

Risk Factors for Glucose Homeostasis

Š‡ ƒ‰‹‰Ǧƒ••‘…‹ƒ–‡† •‡†‡–ƒ”› Ž‹ˆ‡ •–›Ž‡ ƒ† †‹‹‹•Š‡† ’Š›•‹…ƒŽ ƒ…–‹˜‹–› ƒ”‡ ‹’‘”–ƒ– ˆƒ…–‘”• ˆ‘” ƒ‰‡Ǧ”‡Žƒ–‡† …Šƒ‰‡• ‘ˆ‰Ž—…‘•‡Š‘‡‘•–ƒ•‹•Ǥ‡•‡ƒ”…ŠŠƒ••Š‘™–Šƒ–Š‡ƒŽ–Š›‡Ž†‡”Ž› ™‹–Š ‰”‡ƒ–‡” †‡‰”‡‡• ‘ˆ ’Š›•‹…ƒŽ ϐ‹–‡•• Šƒ˜‡ „‡––‡” ‰Ž—…‘•‡ tolerance and lower level of insulin resistance than less active ‘Ž†’‡‘’Ž‡ǤŠ‡•‡Ž‡–ƒŽ—•…Ž‡•ƒ”‡–Š‡ƒŒ‘”•‘—”…‡‘ˆ‰Ž—…‘•‡ —–‹Ž‹œƒ–‹‘Ǥ Ž—…‘•‡‹•–”ƒ•’‘”–‡†‹–‘–Š‡›‘…›–‡•„›‰Ž—…‘•‡ –”ƒ•’‘”–‡”•ǡ Ͷ „‡‹‰ –Š‡ ƒŒ‘” ‰Ž—…‘•‡ –”ƒ•’‘”–‡” ‹ •‡Ž‡–ƒŽ —•…Ž‡ ˆ‘” ‹•—Ž‹Ǧ•–‹—Žƒ–‡† ‰Ž—…‘•‡ —’–ƒ‡Ǥ Š‡ —•…Ž‡ Ͷ’”‘–‡‹Ž‡˜‡Ž‹•‘–ƒŽ–‡”‡†‹‘„‡•‹–›ƒ†ʹǡ „—– ‹–• ‡š’”‡••‹‘ Ž‡˜‡Ž• †‡…Ž‹‡ ™‹–Š ƒ‰‡ ȏͶ͵ȐǤ Š‡ …Šƒ‰‡• in body composition due to decreased lean body mass and contractile strength with age contribute to the reduction in ‹•—Ž‹•–‹—Žƒ–‡†‰Ž—…‘•‡—’–ƒ‡Ǥ ‹ƒŽŽ›ǡ –Š‡ Ž‹ˆ‡•–›Ž‡ ‘†ƒŽ‹–‹‡•ǡ …ƒŽ‘”‹‡ ”‡•–”‹…–‹‘ ȋȌ ƒ† …ƒŽ‘”‹‡ ”‡•–”‹…–‹‘ ™‹–Š ƒ†‡“—ƒ–‡ —–”‹–‹‘ ȋȌ ƒ’’‡ƒ” –‘ ™‘” –Š”‘—‰Š ”‡†—…–‹‘ ‹ ƒ†‹’‘•‡ …‡ŽŽ ƒ•• •’‡…‹ϐ‹…ƒŽŽ›  ǡ ‘š‹†ƒ–‹˜‡ •–”‡•• ƒ† „› ƒ…–‹˜ƒ–‹‰ •‹”–—‹•ǡ ƒ ˆƒ‹Ž› ‘ˆ ‹…‘–‹ƒ‹†‡ ƒ†‡‹‡ †‹—…Ž‡‘–‹†‡Ǧ ȋǦȌ †‡’‡†‡– ’”‘–‡‹ †‡ƒ…‡–›Žƒ•‡• ȏͶͶȐǤ –‡”‡•–‹‰Ž›ǡ ‘˜‡” ‡š’”‡••‹‘ ‘ˆ •‹”–—‹• or treatment with activators of sirtuins, such as resveratrol protects against metabolic decline with aging, increases insulin sensitivity and insulin secretion, improves quality of life and Ž‘‰‡˜‹–›Ǥ

References

1. ƒ––ƒ  ȋʹͲͳͲȌ ›–Š‡•‹•ǡ ‘†‹ϐ‹…ƒ–‹‘ ƒ† —”‘˜‡” ‘ˆ ”‘–‡‹• †—”‹‰ ‰‹‰Ǥ †˜ƒ…‡• ‹ š’‡”‹‡–ƒŽ ‡†‹…‹‡ ƒ† ‹‘Ž‘‰› ͸ͻͶǣ ͳǦͳ͵Ǥ 2. —ƒ•‡ƒ”ƒ ǡ ƒ‘  ȋʹͲͳͳȌ ›’‡ ʹ †‹ƒ„‡–‡• ƒ† –Š‡ ƒ‰‹‰ ’ƒ…”‡ƒ–‹…„‡–ƒ…‡ŽŽǤ‰‹‰͵ȋ͸Ȍǣͷ͸ͷǦͷ͹ͷǤ

3. ‡ƒ˜‡  ȋͳͻͺͺȌ ‘Ž‡ ‘ˆ ‹•—Ž‹ ”‡•‹•–ƒ…‡ ‹ Š—ƒ †‹•‡ƒ•‡Ǥ ‹ƒ„‡–‡•͵͹ȋͳʹȌǣͳͷͻͷǦͳ͸Ͳ͹Ǥ 4. ƒ†‘™ƒ‹  ȋʹͲͲͲȌ •‹‰Š–• ‹–‘ ‹•—Ž‹ ”‡•‹•–ƒ…‡ ƒ† ›’‡ ʹ †‹ƒ„‡–‡•ˆ”‘‘…‘—–‘—•‡‘†‡Ž•Ǥ Ž‹ ˜‡•–ͳͲ͸ȋͶȌǣͶͷͻǦͶ͸ͷǤ 5. ‘‰ǡ—œ—†ƒ”ȋʹͲͳʹȌƒ…”‡ƒ–‹… —…–‹‘ǡ›’‡ʹ‹ƒ„‡–‡•ǡ ƒ†‡–ƒ„‘Ž‹•‹‰‹‰Ǥ –‡”ƒ–‹‘ƒŽ ‘—”ƒŽ‘ˆ†‘…”‹‘Ž‘‰›ͳǦͳ͵Ǥ 6. Šƒ‰ǡƒŽ–‡” ȋʹͲͲ͵Ȍ‰‹‰ƒ†‹•—Ž‹•‡…”‡–‹‘ǤŠ‡ ‘—”ƒŽ‘ˆ Ž‹‹…ƒŽ†‘…”‹‘Ž‘‰›Ƭ‡–ƒ„‘Ž‹•ʹͺͶȋͳȌǣ͹ǦͳʹǤ

How to cite this article: Vinod Nikhra. The Altered Metabolic Homeostasis in Middle Aged and Elderly: Aging and Other Determinants of Insulin Secretion, Action and Resistance. OAJ Gerontol & Geriatric Med. 2018; 3(2): 555608.

Open Access Journal of Gerontology & Geriatric Medicine 7. ƒ•‡›ǡ‹ŽŽ• ǡƒ–‘Šǡ ƒ‹ ȋʹͲͲͺȌ‰‡Ǧƒ••‘…‹ƒ–‡†Ž‘••‘ˆ ‹”–ͳǦ‡†‹ƒ–‡†‡Šƒ…‡‡–‘ˆ‰Ž—…‘•‡Ǧ•–‹—Žƒ–‡†‹•—Ž‹•‡…”‡–‹‘ ‹ „‡–ƒ …‡ŽŽǦ•’‡…‹ϐ‹… ‹”–ͳǦ‘˜‡”‡š’”‡••‹‰ ȋȌ ‹…‡Ǥ ‰‹‰ ‡ŽŽ ͹ȋͳȌǣ͹ͺǦͺͺǤ 8. ‘‘•‡› ǡ ‘—‹Šƒ ǡ Œ‹‘ƒ  ȋʹͲͲͶȌ š‹†ƒ–‹˜‡ •–”‡••ǡ ȾǦ…‡ŽŽ apoptosis, and decreased insulin secretory capacity in mouse models ‘ˆŠ‡‘…Š”‘ƒ–‘•‹•Ǥ†‘…”‹‘Ž‘‰›ͳͶͷȋͳͳȌǣͷ͵ͲͷǦͷ͵ͳʹǤ

9. Š‡†ƒ ǡ ‘Š•‘ ǡ ƒ  ȋͳͻͻ͵Ȍ ʹ ‡š’”‡••‹‘ ƒ† ˆ—…–‹‘ ‹ ȾǦ…‡ŽŽ• ‘ˆ  ”ƒ–• ™‹–Š  ǣ †‹••‘…‹ƒ–‹‘ „‡–™‡‡ ”‡†—…–‹‘• ‹ ‰Ž—…‘•‡ –”ƒ•’‘”– ƒ† ‰Ž—…‘•‡Ǧ•–‹—Žƒ–‡† ‹•—Ž‹ •‡…”‡–‹‘Ǥ‹ƒ„‡–‡•ǡͶʹȋ͹ȌǣͳͲ͸ͷǦͳͲ͹ʹǤ 10. Š–•—„‘ ǡ ƒƒƒ–•— ǡ ‹‘™ƒ  ȋʹͲͲͷȌ ‹‡–ƒ”› ƒ† ‰‡‡–‹… control of glucose transporter 2 glycosylation promotes insulin •‡…”‡–‹‘‹•—’’”‡••‹‰†‹ƒ„‡–‡•Ǥ‡ŽŽͳʹ͵ȋ͹Ȍǣͳ͵Ͳ͹Ǧͳ͵ʹͳǤ

11. Šǡ‘‘ ǡƒ‰ ȋʹͲͲ͹Ȍˆˆ‡…–‘ˆƒ‰‹‰‘‹•—Ž‹•‡…”‡–‘”› ˆ—…–‹‘ ƒ† ‡š’”‡••‹‘ ‘ˆ „‡–ƒ …‡ŽŽ ˆ—…–‹‘Ǧ”‡Žƒ–‡† ‰‡‡• ‘ˆ ‹•Ž‡–•Ǥ ‹ƒ„‡–‡•‡•‡ƒ”…Šƒ†Ž‹‹…ƒŽ”ƒ…–‹…‡͹͹ȋ͵ȌǣͳͷͲǦͳͷͶǤ 12. … —ŽŽ‘…Š  ǡ ˜ƒ †‡ —– ǡ ”ƒ—  ȋʹͲͳͳȌ ʹ ȋʹʹȌ ‹• not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this Ž‘…—•Ǥ‘Ž‡…—Žƒ” ‡‡–‹…•ƒ†‡–ƒ„‘Ž‹•ͳͲͶȋͶȌǣ͸ͶͺǦ͸ͷ͵Ǥ 13. ‡ŽŽ‘ǡ—’‹ǡ’ƒ’‹ƒ–‘ȋʹͲͲͷȌ —…–‹‘ƒŽƒ†‘”’Š‘Ž‘‰‹…ƒŽ ƒŽ–‡”ƒ–‹‘• ‘ˆ ‹–‘…Š‘†”‹ƒ ‹ ’ƒ…”‡ƒ–‹… „‡–ƒ …‡ŽŽ• ˆ”‘ ›’‡ ʹ †‹ƒ„‡–‹…’ƒ–‹‡–•Ǥ‹ƒ„‡–‘Ž‘‰‹ƒͶͺȋʹȌǣʹͺʹǦʹͺͻǤ

14. ”‡•‡ ǡ ƒœ™‹•› ǡ —ŠŽ„ƒ—‡” ǡ ‡•…Š‡  ȋʹͲͲ͹Ȍ ‹”…ƒ†‹ƒ ƒ† ƒ‰‡Ǧ†‡’‡†‡–‡š’”‡••‹‘’ƒ––‡”•‘ˆ ʹƒ†‰Ž—…‘‹ƒ•‡‹–Š‡ ’ƒ…”‡ƒ–‹… „‡–ƒǦ…‡ŽŽ ‘ˆ †‹ƒ„‡–‹… ƒ† ‘†‹ƒ„‡–‹… ”ƒ–•Ǥ ‘”‘‡ ƒ† ‡–ƒ„‘Ž‹…‡•‡ƒ”…Š͵ͻȋͺȌǣͷ͸͹Ǧͷ͹ͶǤ

15. œŠƒ” ǡ ‘ ǡ ‡ƒ˜‡ ǡ ‡ƒ˜‡  ȋͳͻͺ͵Ȍ ˜‹†‡…‡ ‘ˆ ƒ ƒ‰‡Ǧ ”‡Žƒ–‡† †‡…Ž‹‡ ‹ ‹–‘…Š‘†”‹ƒŽ ‰Ž›…‡”‘ŽǦ’Š‘•’Šƒ–‡ †‡Š›†”‘‰‡ƒ•‡ ƒ…–‹˜‹–›‘ˆ‹•‘Žƒ–‡†”ƒ–‹•Ž‡–•Ǥ‡–ƒ„‘Ž‹•͵ʹȋͳͳȌǣͳͲͳͻǦͳͲʹͳǤ 16. ‘ǡ ƒŠ›ǡƒ”ȋͳͻͺ͹ȌŠ‡‡ˆˆ‡…–‘ˆ‰Ž—…‘•‡‘‹•—Ž‹ release and ion movements in isolated pancreatic islets of rats in old ƒ‰‡Ǥ Š›•‹‘Ž͵ͺͶǣ͵Ͷ͹Ǧ͵ͷͶǤ

17. ƒ‡†Ž‡” ǡ …Š—ƒ ǡ …Š—Ž–Š‡••  ȋʹͲͲ͸Ȍ ‰‹‰ …‘””‡Žƒ–‡• ™‹–Š†‡…”‡ƒ•‡†ȾǦ…‡ŽŽ’”‘Ž‹ˆ‡”ƒ–‹˜‡…ƒ’ƒ…‹–›ƒ†‡Šƒ…‡†•‡•‹–‹˜‹–› –‘ ƒ’‘’–‘•‹•ǣ ƒ ’‘–‡–‹ƒŽ ”‘Ž‡ ˆ‘” ƒ• ƒ† ’ƒ…”‡ƒ–‹… †—‘†‡ƒŽ Š‘‡‘„‘šǦͳǤ‹ƒ„‡–‡•ͷͷȋͻȌǣʹͶͷͷǦʹͶ͸ʹǤ

18. —–Ž‡”ǡ ƒ•‘ ǡ‘‡”Ǧ‡‹”ȋʹͲͲ͵ȌȾǦ…‡ŽŽ†‡ϐ‹…‹–ƒ†‹…”‡ƒ•‡† ȾǦ…‡ŽŽƒ’‘’–‘•‹•‹Š—ƒ•™‹–Š–›’‡ʹ†‹ƒ„‡–‡•Ǥ‹ƒ„‡–‡•ͷʹȋͳȌǣͳͲʹǦ ͳͳͲǤ 19. ƒ‡†Ž‡” ǡ ’‹ƒ• ǡ ‡Šƒ  ȋʹͲͲͳȌ Ž—…‘•‡ ‹†—…‡• ȾǦ…‡ŽŽ ƒ’‘’–‘•‹• ˜‹ƒ —’”‡‰—Žƒ–‹‘ ‘ˆ –Š‡ ƒ• ”‡…‡’–‘” ‹ Š—ƒ ‹•Ž‡–•Ǥ ‹ƒ„‡–‡•ͷͲȋͺȌǣͳ͸ͺ͵Ǧͳ͸ͻͲǤ 20. ‡‡”•ǡ”„‡Žǡ•’‘•‹–‘ ȋʹͲͲͻȌ ’ƒ‹”‡†‹•Ž‡––—”‘˜‡”‹Š—ƒ †‘‘”’ƒ…”‡ƒ–ƒ™‹–Šƒ‰‹‰Ǥ—” †‘…”‹‘Žͳ͸ͲȋʹȌǣͳͺͷǦͳͻͳǤ

21. ƒ™ ǡ — ǡ ‹‡ˆˆ‡”   ȋʹͲͳͲȌ ‹ˆˆ‡”‡…‡• „‡–™‡‡ ƒ›Ž‘‹† –‘š‹…‹–› in alpha and beta cells in human and mouse islets and the role of …ƒ•’ƒ•‡Ǧ͵Ǥ‹ƒ„‡–‘Ž‘‰‹ƒͷ͵ȋ͹ȌǣͳͶͳͷǦͳͶʹ͹Ǥ

22. ƒ”” ǡ –œ•…Š‡‹†‡” ǡ —ŽŽ  ȋʹͲͲͶȌ –”ƒǦƒ„†‘‹ƒŽ ˆƒ– ‹• ƒ ƒŒ‘” †‡–‡”‹ƒ– ‘ˆ –Š‡ ƒ–‹‘ƒŽ Š‘Ž‡•–‡”‘Ž †—…ƒ–‹‘ ”‘‰”ƒ †—Ž– ”‡ƒ–‡– ƒ‡Ž  …”‹–‡”‹ƒ ˆ‘” –Š‡ ‡–ƒ„‘Ž‹… •›†”‘‡Ǥ ‹ƒ„‡–‡•ͷ͵ȋͺȌǣʹͲͺ͹ǦʹͲͻͶǤ 23. ”›Š‹ ǡ ‡••‡  ǡ Žƒˆ•‡ ǡ ‹”‡  ȋʹͲͲ͵Ȍ ‰‡ ‘” ™ƒ‹•– ƒ• †‡–‡”‹ƒ–‘ˆ‹•—Ž‹ƒ…–‹‘ǫǤ‡–ƒ„‘Ž‹•ͷʹȋ͹ȌǣͺͷͲǦͺͷ͹Ǥ

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24. ƒ–ƒŽƒ‘ ǡ‡”‰ƒǡ†‡”ȋʹͲͲͷȌ …”‡ƒ•‡†•—•…‡’–‹„‹Ž‹–›–‘ ‹•—Ž‹ ”‡•‹•–ƒ…‡ ƒ••‘…‹ƒ–‡† ™‹–Š ƒ„†‘‹ƒŽ ‘„‡•‹–› ‹ ƒ‰‹‰ ”ƒ–•Ǥ „‡•‡•ͳ͵ȋͳȌǣͳͳǦʹͲǤ 25. —ˆˆƒǡƒ”œ‹Žƒ‹ȋʹͲͲͻȌ‘Ž‡‘ˆ˜‹•…‡”ƒŽƒ†‹’‘•‡–‹••—‡‹ƒ‰‹‰Ǥ ‹‘…Š‹‹‘’Š›•…–ƒͳ͹ͻͲȋͳͲȌǣͳͳͳ͹Ǧͳͳʹ͵Ǥ

26. ƒ„”‹‡Ž› ǡ ƒ ǡ ƒ‰  ȋʹͲͲʹȌ ‡‘˜ƒŽ ‘ˆ ˜‹•…‡”ƒŽ ˆƒ– ’”‡˜‡–• ‹•—Ž‹ ”‡•‹•–ƒ…‡ ƒ† ‰Ž—…‘•‡ ‹–‘Ž‡”ƒ…‡ ‘ˆ ƒ‰‹‰ǣ ƒ ƒ†‹’‘‹‡Ǧ ‡†‹ƒ–‡†’”‘…‡••ǫǤ‹ƒ„‡–‡•ͷͳȋͳͲȌǣʹͻͷͳǦʹͻͷͺǤ

27. ‡‹Ž„”‘ǡƒ˜—••‹ȋʹͲͲ͵ȌƒŽ‘”‹‡”‡•–”‹…–‹‘ƒ†ƒ‰‹‰ǣ”‡˜‹‡™ ‘ˆ–Š‡Ž‹–‡”ƒ–—”‡ƒ†‹’Ž‹…ƒ–‹‘•ˆ‘”•–—†‹‡•‹Š—ƒ•Ǥ Ž‹—–” ͹ͺȋ͵Ȍǣ͵͸ͳǦ͵͸ͻǤ

28. —œ—†ƒ”ǡŽŽ‹•‘ǡ—ˆˆƒʹͲͲͺǤ‹•…‡”ƒŽƒ†‹’‘•‡–‹••—‡ ‘†—Žƒ–‡•ƒƒŽ‹ƒŽ‘‰‡˜‹–›Ǥ‰‹‰‡ŽŽ͹ȋ͵ȌǣͶ͵ͺǦͶͶͲǤ

29. ‡”•Šƒ™ǡ Ž‹‡” ȋʹͲͲͶȌ†‹’‘•‡–‹••—‡ƒ•ƒ‡†‘…”‹‡‘”‰ƒǤ  Ž‹†‘…”‹‘Ž‡–ƒ„ͺͻȋ͸ȌǣʹͷͶͺǦʹͷͷ͸Ǥ

30. Ž˜‡Š—•ǡ—”‡ ǡŒ‘•–”‘ȋʹͲͳͲȌŠ‡Š—ƒ˜‹•…‡”ƒŽˆƒ–†‡’‘– Šƒ•ƒ—‹“—‡‹ϐŽƒƒ–‘”›’”‘ϐ‹Ž‡Ǥ„‡•‹–›ͳͺȋͷȌǣͺ͹ͻǦͺͺ͵Ǥ 31. ƒ—‡Ž ǡ ‡–‡”•‡  ǡ Š—Žƒ  ȋʹͲͳͲȌ ‹’‹†Ǧ‹†—…‡† ‹•—Ž‹ ”‡•‹•–ƒ…‡ǣ —”ƒ˜‡ŽŽ‹‰ –Š‡ ‡…Šƒ‹•Ǥ ƒ…‡– ͵͹ͷȋͻ͹͵͵Ȍǣ ʹʹ͸͹Ǧ ʹʹ͹͹Ǥ

32. ‘…Šǡ—†‡”Ž‹…Š ǡ‡‹„Ž‡” ȋʹͲͲͺȌ‡–”ƒŽ‹•—Ž‹ƒ…–‹‘”‡‰—Žƒ–‡• ’‡”‹’Š‡”ƒŽ‰Ž—…‘•‡ƒ†ˆƒ–‡–ƒ„‘Ž‹•‹‹…‡Ǥ Ž‹ ˜‡•–ͳͳͺȋ͸Ȍǣ ʹͳ͵ʹǦʹͳͶ͹Ǥ 33. ‡ŽŽ‹‰ǡ‘”–‘

ǡ‘””‹•‘ȋʹͲͲ͸Ȍ •—Ž‹ƒ…–‹‘‹–Š‡„”ƒ‹ …‘–”‹„—–‡•–‘‰Ž—…‘•‡Ž‘™‡”‹‰†—”‹‰‹•—Ž‹–”‡ƒ–‡–‘ˆ†‹ƒ„‡–‡•Ǥ ‡ŽŽ‡–ƒ„͵ȋͳȌǣ͸͹Ǧ͹͵Ǥ

34. ‡˜ƒ ǡ …Š—„‡”–  ȋʹͲͳͳȌ ‡–”ƒŽ ‹•—Ž‹ ƒ† ‹•—Ž‹ǦŽ‹‡ ‰”‘™–Š ˆƒ…–‘”Ǧͳ•‹‰ƒŽ‹‰ǣ‹’Ž‹…ƒ–‹‘•ˆ‘”†‹ƒ„‡–‡•ƒ••‘…‹ƒ–‡††‡‡–‹ƒǤ—”” ‹ƒ„‡–‡•‡˜͹ȋͷȌǣ͵ͷ͸Ǧ͵͸͸Ǥ 35. –‡‡ǡ‡””›ǡ‹˜‡”ƒ ȋʹͲͲͷȌ ’ƒ‹”‡†‹•—Ž‹ƒ†‹•—Ž‹ǦŽ‹‡ ‰”‘™–Š ˆƒ…–‘” ‡š’”‡••‹‘ ƒ† •‹‰ƒŽ‹‰ ‡…Šƒ‹•• ‹ ŽœŠ‡‹‡”ǯ• †‹•‡ƒ•‡Ǧ‹•–Š‹•–›’‡͵†‹ƒ„‡–‡•ǫǤ ŽœŠ‡‹‡”ǯ•†‹•͹ȋͳȌǣ͸͵ǦͺͲǤ 36. ”ƒˆ– ǡ ƒ‡” ǡ ‘–‹‡   ȋʹͲͳʹȌ –”ƒƒ•ƒŽ ‹•—Ž‹ –Š‡”ƒ’› ˆ‘” ŽœŠ‡‹‡” †‹•‡ƒ•‡ ƒ† ƒ‡•–‹… ‹Ž† …‘‰‹–‹˜‡ ‹’ƒ‹”‡–ǣ ƒ ’‹Ž‘– …Ž‹‹…ƒŽ–”‹ƒŽǤ”…Š‡—”‘Ž͸ͻȋͳȌǣʹͻǦ͵ͺǤ 37. …ƒŽŽȋʹͲͲʹȌ‹ƒ„‡–‡•‡ŽŽ‹–—•ƒ†–Š‡…‡–”ƒŽ‡”˜‘—••›•–‡Ǥ –‡”ƒ–‹‘ƒŽ‡˜‡—”‘„‹‘ŽͷͳǣͶͳͷǦͶͷ͵Ǥ 38. ‡”ƒ†‡•ǡƒƒ† ǡ‡ŽŽ‘•‘ȋʹͲͲͳȌˆˆ‡…–•‘ˆƒ‰‡‘‡Ž‡‡–• ‘ˆ ‹•—Ž‹Ǧ•‹‰ƒŽ‹‰ ’ƒ–Š™ƒ› ‹ …‡–”ƒŽ ‡”˜‘—• •›•–‡ ‘ˆ ”ƒ–•Ǥ †‘…”‹‡ͳ͸ȋ͵Ȍǣʹʹ͹Ǧʹ͵ͶǤ

39. ƒ‰ǡƒǡ‡‡ȋʹͲͲͳȌŠ‡”‘Ž‡‘ˆŽ‡’–‹”‡•‹•–ƒ…‡‹–Š‡ Ž‹’‹†ƒ„‘”ƒŽ‹–‹‡•‘ˆƒ‰‹‰Ǥ  ͳͷȋͳȌǣͳͲͺǦͳͳͶǤ

40. ‹œ‹”‹ ǡ ƒ”†‘œ‘ ǡ ‘’  ȋʹͲͲͺȌ Š‡ ”‘Ž‡ ˆ‘” ‡†‘’Žƒ•‹… ”‡–‹…—Ž—•–”‡••‹†‹ƒ„‡–‡•‡ŽŽ‹–—•Ǥ†‘…”‡˜ʹͻȋͳȌǣͶʹǦ͸ͳǤ 41. ‡””ƒ‹‹ ǡ ‹…Š‹ ǡ ‡…Ǧ‹‡Ž•‡  ȋͳͻͻ͸Ȍ •—Ž‹ ƒ…–‹‘ ƒ† ƒ‰‡ǡ —”‘’‡ƒ ”‘—’ˆ‘”–Š‡–—†›‘ˆ •—Ž‹‡•‹•–ƒ…‡ȋ ȌǤ‹ƒ„‡–‡• Ͷͷȋ͹ȌǣͻͶ͹Ǧͻͷ͵Ǥ

42. ‘—ƒ”† ǡ ‡‹†‡” ǡ ‘Žƒ  ȋͳͻͻͷȌ ‡Ž‡–ƒŽ —•…Ž‡ Ͷ ’”‘–‡‹…‘…‡–”ƒ–‹‘ƒ†ƒ‰‹‰‹Š—ƒ•Ǥ‹ƒ„‡–‡•ͶͶȋͷȌǣͷͷͷǦͷ͸ͲǤ 43. —ƒ”‡–‡ǡ‹…ƒ”† ȋʹͲͲͷȌƒŽ‘”‹‡”‡•–”‹…–‹‘ǦǦŠ‡ ʹ…‘‡…–‹‘Ǥ ‡ŽŽͳʹͲȋͶȌǣͶ͹͵ǦͶͺʹǤ

44. ƒ‹ ǡ —ƒ”‡–‡  ȋʹͲͳͶȌ Ϊ ƒ† •‹”–—‹• ‹ ƒ‰‹‰ ƒ† †‹•‡ƒ•‡Ǥ ”‡†•‡ŽŽ‹‘ŽʹͶȋͺȌǣͶ͸ͶǦͶ͹ͳǤ

How to cite this article: Vinod Nikhra. The Altered Metabolic Homeostasis in Middle Aged and Elderly: Aging and Other Determinants of Insulin Secretion, Action and Resistance. OAJ Gerontol & Geriatric Med. 2018; 3(2): 555608.