Effects of Acarbose on the Acceleration of Postprandial Hyperglycemia–Induced Pathological Changes Induced by Intermittent Hypoxia in Lean Mice

Miyamura, Masatoshi; Schnell, Oliver; Yamashita, Chika; Yoshioka, Toshitaka; Matsumoto, Chika; Mori, Tatsuhiko; Ukimura, Akira; Kitaura, Yasushi; Matsumura, Yasuo; Ishizaka, Nobukazu; Hayashi, Toshio

doi:10.1254/jphs.10014fp

Cited by 16 publications

(8 citation statements)

References 44 publications

(41 reference statements)

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“…This spike is reduced by ACA (Balfour & McTavish, ). Acarbose has been used clinically to prevent postprandial hyperglycemia for many years, and there are several reports showing its ability to limit or prevent postprandial hyperglycemia in mice as well (Frantz et al ., ; Kim et al ., ; Miyamura et al ., ). The glucose spike during a meal is blunted because acarbose inhibits α‐glucosidases in the intestine, thereby slowing the digestion of starches and disaccharides to glucose.…”

Section: Introductionmentioning

confidence: 97%

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

et al. 2013

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Four agents — acarbose (ACA), 17-α-estradiol (EST), nordihydroguaiaretic acid (NDGA), and methylene blue (MB) — were evaluated for lifespan effects in genetically heterogeneous mice tested at three sites. Acarbose increased male median lifespan by 22% (P < 0.0001), but increased female median lifespan by only 5% (P = 0.01). This sexual dimorphism in ACA lifespan effect could not be explained by differences in effects on weight. Maximum lifespan (90th percentile) increased 11% (P < 0.001) in males and 9% (P = 0.001) in females. EST increased male median lifespan by 12% (P = 0.002), but did not lead to a significant effect on maximum lifespan. The benefits of EST were much stronger at one test site than at the other two and were not explained by effects on body weight. EST did not alter female lifespan. NDGA increased male median lifespan by 8–10% at three different doses, with P-values ranging from 0.04 to 0.005. Females did not show a lifespan benefit from NDGA, even at a dose that produced blood levels similar to those in males, which did show a strong lifespan benefit. MB did not alter median lifespan of males or females, but did produce a small, statistically significant (6%, P = 0.004) increase in female maximum lifespan. These results provide new pharmacological models for exploring processes that regulate the timing of aging and late-life diseases, and in particular for testing hypotheses about sexual dimorphism in aging and health.

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Section: Introductionmentioning

confidence: 97%

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

et al. 2013

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“…This spike is reduced by ACA (Balfour & McTavish, ). Acarbose has been widely used clinically to prevent postprandial hyperglycemia, and several reports (Frantz et al, ; Miyamura et al, ) demonstrate its ability to reduce or prevent postprandial hyperglycemia in mice. The glucose spike during a meal is blunted because acarbose inhibits α‐glucosidase, thus reducing the rate at which polysaccharides are digested, as well as reducing sugar uptake.…”

Section: Introductionmentioning

confidence: 99%

Acarbose improves health and lifespan in aging HET3 mice

et al. 2019

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To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log‐rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2‐(2‐hydroxyphenyl) benzothiazole (HBX), and INT‐767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans.

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“…This was also supported by animal studies in which exposure to acarbose was associated both with prevention of cardiac interstitial fibrosis and cardiomyocyte hypertrophy in a model of intermittent hypoxia. 42 The landmark Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial evaluated the efficacy of 3 years of treatment with acarbose vs. placebo in preventing the transition to overt diabetes among 1429 patients with IGT. 43 Targeting postprandial hyperglycaemia with acarbose was not only found to be associated with a 36% reduction of new onset diabetes, but also with a highly significant reduction of myocardial infarction (1 vs. 12, p = 0.0226) and any CV event (15 vs. 32, p = 0.0326) as assessed by a post hoc analysis of secondary outcomes (Figure 3).…”

Section: Intervening On Postprandial Hyperglycaemia: Acute and Longermentioning

confidence: 99%

Alpha-glucosidase inhibitors 2012 – cardiovascular considerations and trial evaluation

Standl¹,

Schnell²

2012

Diabetes and Vascular Disease Research

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Alpha-glucosidase inhibitors have been available for clinical use for about 20 years. They have shown reasonably good efficacy comparable to other oral blood glucose lowering drugs and in some parts of the world are the most commonly prescribed oral diabetes medication, especially in Asian countries. Unlike as has been observed with some other blood glucose lowering agents, however, no adverse signals of potential cardiovascular harm have emerged in relation to their use. On the contrary, significant beneficial cardiovascular outcome results have been observed in the post-hoc analyses of randomised placebo-controlled trials with the alpha-glucosidase inhibitor acarbose. Targeting mainly postprandial hyperglycaemia, alpha-glucosidase inhibitors favourably affect several cardiovascular risk factors, such as obesity, hypertension and high glycaemic variability with little to no risk for hypoglycaemia. Furthermore, acarbose favourably affects endothelial dysfunction and carotid intima media thickening in humans and, in animal models, improves cardiac interstitial fibrosis and hypertrophy of cardiomyocytes. The ultimate determination of the cardiovascular effects of alpha-glucosidase inhibitors in terms of clinical outcomes awaits the results of ongoing long-term, randomised, placebocontrolled trials.

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Effects of Acarbose on the Acceleration of Postprandial Hyperglycemia–Induced Pathological Changes Induced by Intermittent Hypoxia in Lean Mice

Cited by 16 publications

References 44 publications

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

Acarbose, 17‐α‐estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males

Acarbose improves health and lifespan in aging HET3 mice

Alpha-glucosidase inhibitors 2012 – cardiovascular considerations and trial evaluation

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