Involvement of low adiponectin levels in impaired glucose tolerance

Nakashima, Youhei; Inukai, Kouichi; Imai, Kenta; Ikegami, Yuichi; Awata, Takuya; Katayama, Shigehiro

doi:10.1016/j.metabol.2008.05.001

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…It is known that NO-mediated increase in TNF-α or free fatty acid caused suppression of insulin secretion and insulin resistance (31) and that low levels of adiponectin were associated with impaired glucose tolerance and the development of type 2 diabetes (32). Our studies found that serum adiponectin concentrations were significantly decreased in HBx Tg mice when compared with WT mice (Table 1), whereas TNF-α and free fatty acid were significantly increased (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus X Protein Regulates Hepatic Glucose Homeostasis via Activation of Inducible Nitric Oxide Synthase

Shin

Park

Kim

et al. 2011

Journal of Biological Chemistry

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Dysregulation of liver functions leads to insulin resistance causing type 2 diabetes mellitus and is often found in chronic liver diseases. However, the mechanisms of hepatic dysfunction leading to hepatic metabolic disorder are still poorly understood in chronic liver diseases. The current work investigated the role of hepatitis B virus X protein (HBx) in regulating glucose metabolism. We studied HBx-overexpressing (HBxTg) mice and HBxTg mice lacking inducible nitric oxide synthase (iNOS). Here we show that gene expressions of the key gluconeogenic enzymes were significantly increased in HepG2 cells expressing HBx (HepG2-HBx) and in non-tumor liver tissues of hepatitis B virus patients with high levels of HBx expression. In the liver of HBxTg mice, the expressions of gluconeogenic genes were also elevated, leading to hyperglycemia by increasing hepatic glucose production. However, this effect was insufficient to cause systemic insulin resistance. Importantly, the actions of HBx on hepatic glucose metabolism are thought to be mediated via iNOS signaling, as evidenced by the fact that deficiency of iNOS restored HBx-induced hyperglycemia by suppressing the gene expression of gluconeogenic enzymes. Treatment of HepG2-HBx cells with nitric oxide (NO) caused a significant increase in the expression of gluconeogenic genes, but JNK1 inhibition was completely normalized. Furthermore, hyperactivation of JNK1 in the liver of HBxTg mice was also suppressed in the absence of iNOS, indicating the critical role for JNK in the mutual regulation of HBx- and iNOS-mediated glucose metabolism. These findings establish a novel mechanism of HBx-driven hepatic metabolic disorder that is modulated by iNOS-mediated activation of JNK.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus X Protein Regulates Hepatic Glucose Homeostasis via Activation of Inducible Nitric Oxide Synthase

Shin

Park

Kim

et al. 2011

Journal of Biological Chemistry

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“…For glucose tolerance tests, mice were fasted for 8 hr and 10% glucose solution was administered intraperitoneally (2 mg/g body for wild type mice, 1.5 mg/g·body for diabetic mice) as previously described [13]. Glucose measurements were conducted before injection, and at 30, 60, and 120 min after injection.…”

Section: Methodsmentioning

confidence: 99%

Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice

et al. 2014

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We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.

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“…The pathophysiology underlying the previously reported association in the literature is not fully elucidated [ 27 ]. It appears that adiponectin improves insulin sensitivity by increasing fatty acid oxidation in muscle, and affects glucose homeostasis by suppressing hepatic glucose production [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

“…People with IGT represent an asymptomatic subpopulation with increased CVD risk [ 31 ] and there is evidence to suggest that increased risk for CVD observed in IGT is due, at least in part, to lower-than-normal levels of adiponectin [ 27 ; 32 ]. Ko et al investigated the discriminatory performance of adiponectin jointly with waist circumference in middle-aged males [ 15 ]; yet, that analysis did not include females or leptin.…”

Section: Discussionmentioning

confidence: 99%

Discriminatory performance of adiponectin and leptin in the identification of impaired glucose tolerance: The Guangzhou Biobank Cohort Study - Cardiovascular Disease Subcohort

Toulis

Jiang²,

Hemming

et al. 2018

PLoS ONE

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BackgroundTo evaluate the additional discriminatory performance of adiponectin, leptin, and their ratio in the identification of impaired glucose tolerance (IGT) in men and women without diabetes on top of conventional risk factors.Methods & resultsA total of 698 subjects underwent an oral glucose tolerance test (oGTT) and adipocytokine measurements. A comprehensive stepwise selection procedure was performed, followed by c-statistics and integrated discrimination improvement (IDI) analysis. In males, adiponectin levels were significantly lower in the IGT group compared to the non-IGT group (Whitney U test, p < 10–4), whereas leptin levels were significantly higher (p = 0.009) in IGT group. In females, adiponectin and leptin levels were not significantly different between groups (Mann-Whitney U test, p = 0.073 and p = 0.08, respectively). Adjusting for the most informative, sex-specific, clinical and biochemical factors, adiponectin, leptin and their ratio were not found to be significant predictors of the response to the glucose load, when modelled as continuous terms or tertiles. In males, the area-under-the-curve (AUC) for adiponectin was estimated at 0.620 (95% CI: 0.558–0.682) and the addition of adiponectin into the basic model provided a ΔAUC benefit of 0.004, showing no additional discriminatory benefit on top of conventional risk factors (IDI p-value: 0.27), nor did the addition of leptin or their ratio. The results were similar in females.ConclusionsIn Chinese individuals without diabetes, no significant evidence for the potential discriminatory value of adiponectin, leptin or their ratio in the identification of IGT on top of conventional risk factors was observed.

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Involvement of low adiponectin levels in impaired glucose tolerance

Cited by 8 publications

References 32 publications

Hepatitis B Virus X Protein Regulates Hepatic Glucose Homeostasis via Activation of Inducible Nitric Oxide Synthase

Hepatitis B Virus X Protein Regulates Hepatic Glucose Homeostasis via Activation of Inducible Nitric Oxide Synthase

Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice

Discriminatory performance of adiponectin and leptin in the identification of impaired glucose tolerance: The Guangzhou Biobank Cohort Study - Cardiovascular Disease Subcohort

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