Biochemical and Biophysical Research Communications
Resistin induces insulin resistance in pancreatic islets to impair glucose-induced insulin release
Section snippets
Materials and methods
Animals. Adult male ICR mice 8-weeks-old and weighing ∼35 g were purchased from Japan Charles River (Yokohama, Japan) and maintained at a constant temperature, humidity, and light cycle with food and water ad libitum. The animal protocols were approved by the Jichi Medical School Institute of Animal Care and Use Committee and were in accord with the Japanese Physiological Society’s guidelines for animal care.
Recombinant adenoviral vectors. A fragment of mouse resistin cDNA was amplified by
Resistin expression in plasma
By Western blot analysis, resistin was detected in the plasma of the Adeno-Res, but not LacZ, injected mice at day 2 after injection (Fig. 1A). Adeno-Res injection increased plasma resistin concentration approximately by 2.5-fold (Fig. 1B).
Blood glucose concentration under fed conditions was elevated at day 2 in resistin injected mice (215.2 ± 8.7 mg/dl with resistin vs. 135.4 ± 11.6 mg/dl with LacZ; P < 0.001) and the elevated level declined later. The result suggested that the expression of resistin
Discussion
Resistin, a polypeptide released from adipocytes, can exert systemic effects on insulin sensitivity, lipid metabolism, and inflammatory processes [2], [8]. It has been shown that resistin affects glucose metabolism in the liver and skeletal muscle by attenuating insulin action [3], [4], [5], [9]. We aimed to explore the systemic effects of resisitin, independently of obesity, on the glucose metabolism and pancreatic islets. For this, we developed a non-obese mouse model overexpressing resistin
Acknowledgments
We thank Tamie Miyoshi and Miyoko Mistu for expert technical assistance. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to M.N., T.O., K.O., and T.Y.), that on Priority Areas (15081101) (T.Y.), a grant from the 21st century Center of Excellence program (T.Y. and K.O.), an Insulin Research Award from Novo Nordisk Pharma Ltd. (T.Y.), and a grant from Japan Diabetes Foundation (T.T.).
References (25)
- et al.
Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat
J. Biol. Chem.
(2003) - et al.
Leptin potentiates ADP-induced [Ca2+]i increase via JAK2 and tyrosine kinases in a megakaryoblast cell line
Diabetes Res. Clin. Pract.
(2005) - et al.
Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes
Cell
(1999) - et al.
Enzyme-linked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes
Clin. Chim. Acta
(2004) - et al.
Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro
Biochem. Biophys. Res. Commun.
(2003) - et al.
Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators
Biochem. Biophys. Res. Commun.
(2003) - et al.
Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway
Biochem. Biophys. Res. Commun.
(2005) Role of insulin resistance in human
Diabetes
(1988)- et al.
The hormone resistin links obesity to diabetes
Nature
(2001) - et al.
Adenovirus-mediated chronic “hyper-resistinemia” leads to in vivo insulin resistance in normal rats
J. Clin. Invest.
(2004)
Role of resistin in diet-induced hepatic insulin resistance
J. Clin. Invest.
Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production
J. Clin. Invest.
Cited by (63)
Resistin in endocrine pancreas of sheep: Presence and expression related to different diets
2024, General and Comparative EndocrinologyActivation of the porcine alveolar macrophages via toll-like receptor 4/NF-κB mediated pathway provides a mechanism of resistin leading to inflammation
2018, CytokineCitation Excerpt :Resistin, a cysteine-rich adipokine, is primarily investigated in mice adipocytes, which is originally proposed as a negative regulator of insulin [1–3].
Gut microbiota in obesity and undernutrition
2016, Advances in NutritionMicrobiota and Glucidic Metabolism: A Link with Multiple Aspects and Perspectives
2023, International Journal of Molecular Sciences