The α-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic β-cells in OLETF rats

Fukaya, Nanae; Mochizuki, Kazuki; Tanaka, Yutaro; Kumazawa, Takao; Zhu, Jiuxin; Fuchigami, Masahiro; Goda, Toshinao

doi:10.1016/j.ejphar.2009.09.048

Cited by 33 publications

(18 citation statements)

References 25 publications

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“…Plasma variables were measured after a 5-h fast and in many cases do not represent fully fasted values. Together with issues such as stressful transport of animals between buildings before death, this likely contributes to the elevation of plasma glucose in LSED animals compared with those in previous reports (18,20). LSED animals are not chronically hyperglycemic at 20 wk of age, however, as demonstrated by normal HbA1c levels (4.6% vs. 5.4% in OSED, P Ͻ 0.05) (39).…”

Section: Animal Characteristicsmentioning

confidence: 45%

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Bender

Newcomer

Laughlin

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Functional and structural heterogeneity exists among skeletal muscle vascular beds related, in part, to muscle fiber type composition. This study was designed to delineate whether the vulnerability to vascular dysfunction in insulin resistance is uniformly distributed among skeletal muscle vasculatures and whether physical activity modifies this vulnerability. Obese, hyperphagic Otsuka Long-Evans Tokushima fatty rats (20 wk old) were sedentary (OSED) or physically active (OPA; access to running wheels) and compared with age-matched sedentary Long-Evans Tokushima Otsuka (LSED) rats. Vascular responses were determined in isolated, pressurized feed arteries from fast-twitch gastrocnemius (GFAs) and slow-twitch soleus (SFAs) muscles. OSED animals were obese, insulin resistant, and hypertriglyceridemic, traits absent in LSED and OPA rats. GFAs from OSED animals exhibited depressed dilation to ACh, but not sodium nitroprusside, and enhanced vasoconstriction to endothelin-1 (ET-1), but not phenylephrine, compared with those in LSED. Immunoblot analysis suggests reduced endothelial nitric oxide synthase phosphorylation at Ser1177 and endothelin subtype A receptor expression in OSED GFAs. Physical activity prevented reduced nitric oxide-dependent dilation to ACh, but not enhanced ET-1 vasoconstriction, in GFA from OPA animals. Conversely, vasoreactivity of SFAs to ACh and ET-1 were principally similar in all groups, whereas dilation to sodium nitroprusside was enhanced in OSED and OPA rats. These data demonstrate, for the first time, that SFAs from insulin-resistant rats exhibit reduced vulnerability to dysfunction versus GFAs and that physical activity largely prevents GFA dysfunction. We conclude that these results demonstrate that vascular dysfunction associated with insulin resistance is heterogeneously distributed across skeletal muscle vasculatures related, in part, to muscle fiber type and activity level.

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Section: Animal Characteristicsmentioning

confidence: 45%

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Bender

Newcomer

Laughlin

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…The applied dose of miglitol is determined on the basis of doses with lower incidence of digestive symptoms such as diarrhea and with potency for reducing postprandial hyperglycemia. Previous studies have demonstrated that doses of 400 and 800 ppm in the diet did not cause the incidence of digestive symptoms in rats (25,35). In this study, we did not observe digestive symptoms in the OLETF rats fed a diet containing 600 ppm miglitol.…”

Section: Discussionsupporting

confidence: 31%

“…Generally, suppression of insulin secretion by inhibition of postprandial hyperglycemia protects against apoptosis of pancreatic b-cells and maintains the insulin secretion capacity. Indeed, we reported that long-term treatment with miglitol in OLETF rats maintained the capacity of insulin secretion and reduced the development of type 2 diabetes (25). These findings indicate that miglitol has potency to protect the insulin secretion capacity of pancreatic b-cells by reducing postprandial insulin secretion.…”

Section: Discussionmentioning

confidence: 62%

Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats

Imai

Harazaki

Inoue

et al. 2015

J Nutr Sci Vitaminol

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Recent cohort studies such as Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) in Europe and FUNAGATA in Japan have demonstrated that postprandial hyperglycemia is a strong independent risk factor for the development of cardiovascular diseases (CVD) in subjects with impaired glucose tolerance (IGT), reflecting pre-diabetic subjects, or type 2 diabetes (1, 2). Furthermore, the Study To Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial reported that suppression of postprandial hyperglycemia in subjects with IGT, the pre-diabetic stage, by treatment with the a-glucosidase inhibitor (a-GI) acarbose, which suppresses postprandial hyperglycemia by inhibiting the carbohydrate digestion in the small intestine, reduces the incidence of CVD as well as the development of type 2 diabetes (3). These lines of evidence indicate that inhibition of postprandial hyperglycemia from the pre-diabetic stage could inhibit CVD development.Many previous studies have shown that CVDs are related to activation of leukocytes such as neutrophils, monocytes, and macrophages, and associated disorders of vascular endothelial function. Postprandial hyperglycemia activates the leukocytes through the production of reactive oxygen species (ROS) by activated neutrophils and enhanced glucose metabolism in mitochondria (4). The activated leukocytes secrete inflammatory cytokines such as interleukin (IL)-1b and tumor necrosis factor (TNF)-a (5, 6). These inflammatory cytokines Summary It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an a-glucosidase inhibitor (a-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an a-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1b, tumor necrosis factor-a, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory ...

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“…The blood insulin level in the ZDF rat increases to compensate for insulin resistance until 10 weeks of age and then decreases along with the progressive dysfunction of pancreatic ␤-cells (Sugimoto et al, 2008). Several studies have shown that jpet.aspetjournals.org pharmacological treatment to control hyperglycemia results in preservation of pancreatic ␤-cells in rodent models (Koyama et al, 2000;Fukaya et al, 2009). For example, an ␣-glucosidase inhibitor preserves pancreatic ␤-cells in GotoKakizaki rats, a model for type 2 diabetes (Goda et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

KGA-2727, a Novel Selective Inhibitor of a High-Affinity Sodium Glucose Cotransporter (SGLT1), Exhibits Antidiabetic Efficacy in Rodent Models

Shibazaki

Tomae²,

Ishikawa-Takemura³

et al. 2012

J Pharmacol Exp Ther

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The α-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic β-cells in OLETF rats

Cited by 33 publications

References 25 publications

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats

KGA-2727, a Novel Selective Inhibitor of a High-Affinity Sodium Glucose Cotransporter (SGLT1), Exhibits Antidiabetic Efficacy in Rodent Models

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The α-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic β-cells in OLETF rats

Cited by 33 publications

References 25 publications

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Differential vulnerability of skeletal muscle feed arteries to dysfunction in insulin resistance: impact of fiber type and daily activity

Treatment with DPP-4I Anagliptin or &alpha;-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats

KGA-2727, a Novel Selective Inhibitor of a High-Affinity Sodium Glucose Cotransporter (SGLT1), Exhibits Antidiabetic Efficacy in Rodent Models

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Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats