Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Zilverschoon, G R C; Tack, Cees J.; Joosten, Leo A. B.; Kullberg, Bart Jan; Meer, J.W.M. van der; Netea, Mihai G.

doi:10.1038/ijo.2008.109

Cited by 61 publications

(53 citation statements)

References 35 publications

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“…Some reports have shown that increased circulating IL-18 or genetic variation of IL-18 is linked with insulin resistance in patients with type 2 diabetes mellitus, obesity, or polycystic ovary syndrome [14,15,24,25]. By contrast, our study identified insulin resistance during acute endotoxemia only in the absence of IL-18.…”

Section: Discussioncontrasting

confidence: 50%

Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Yamashita

Ishikawa

Takahara

et al. 2015

Surgical Infections

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Background: Hyperglycemia associated with insulin resistance is common among critically ill patients. Interleukin (IL)-18 has been linked with hyperglycemia and insulin resistance in chronic disease, but the relation between IL-18 and insulin resistance during critical illness was unexplored. This study investigated whether IL-18 modulates hyperglycemia and insulin resistance during acute inflammation. Methods: We injected lipopolysaccharide (LPS) 40 mg/kg into wild-type (WT) and IL-18 knockout (KO) mice to induce endotoxemia and examined insulin resistance and insulin-dependent signaling pathways during the acute phase. Results: During the first hour after LPS treatment, IL-18 KO mice showed higher blood glucose and insulin and less insulin receptor substrate-1 and less phosphorylated Akt in the liver compared with WT mice. Interleukin-18 KO mice exhibited better survival after LPS treatment. Conclusions: The findings suggest that endogenous IL-18 may attenuate hyperglycemia and modulate insulin signaling in liver. Accordingly, IL-18 may modulate glucose tolerance during acute inflammation.

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Section: Discussioncontrasting

confidence: 50%

Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Yamashita

Ishikawa

Takahara

et al. 2015

Surgical Infections

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“…IL-18 is also known to have a proinflammatory effect in systemic lupus erythematosus [32,33]. Increases in both the serum levels of, and resistance to, IL-18 have been reported in obese type 2 patients with diabetes [34]. Moreover, IL-18 has been reported to play a role in the formation of inflammation and endothelial dysfunction [35], and Wong et al [36] reported that IL-18 was involved in renal dysfunction in non-diabetic patients.…”

Section: Discussionmentioning

confidence: 96%

Interleukin-18 contributes more closely to the progression of diabetic nephropathy than other diabetic complications

et al. 2010

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Diabetic complication is comprised of a wide variety of pathophysiological factors involving proinflammatory cytokines, adipokines, and oxidative stress, among others. Each of these complications differs in their incidence and the stage of their occurrence. We examined cytokines and stress markers in 48 patients with type 2 diabetes mellitus and compared the difference of their contribution to pathogenesis between nephropathy and other diabetic complications. Hemoglobin A1c correlated with the level of low-density lipoprotein-cholesterol, and significantly elevated in the severe macroangiopathy group. Cystatin C increased in the severe microangiopathy groups but did not increase in the macroangiopathy group. The levels of interleukin 18 (IL-18), high-sensitive CRP (H-CRP), liver-type fatty acid binding protein, and 8-hydroxy-2-deoxyguanosine increased in the severe microangiopathy group. These data suggest the participation of proinflammatory signaling and oxidative stress in the progression of microangiopathy. In particular, IL-18 and H-CRP were significantly elevated only in the severe nephropathy group but did not significantly elevate in other complications. These data suggest another effect of IL-18 on glomerulus in addition to its proinflammatory effect. In conclusion, we propose that IL18 has a specific role that contributes more closely to the progression of diabetic nephropathy than other diabetic complications.

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“…Increasing concentrations of the cytokine in these patients predict increased risk for nephropathy and retinopathy. It has been suggested that the patients develop resistance to IL-18, as their PBMC produce less IFN-c in response to exogenous IL-18 as compared with the cells from healthy control subjects [64]. Clearly, further studies are required to investigate this issue.…”

Section: Metabolic Effectsmentioning

confidence: 98%

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

et al. 2016

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Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Cited by 61 publications

References 35 publications

Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Endogenous Interleukin 18 Suppresses Hyperglycemia and Hyperinsulinemia during the Acute Phase of Endotoxemia in Mice

Interleukin-18 contributes more closely to the progression of diabetic nephropathy than other diabetic complications

Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection

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