Hyperglycaemia due to insulin resistance caused by interferon-γ

Abstract

Marked hyperglycaemia (30.9 mmol l −1 ) during interferon-␥ (IFN-␥) therapy for asymptomatic recurrent renal cancer as multiple lung metastases in a 52-year-old man is described. Although the involvement of IFN-␥ has been reported in the development of autoimmune diabetes, in this case, antibodies against pancreatic ␤-cells including anti-islet cell antibody (ICA) and anti-glutamic acid decarboxylase (GAD) antibody were negative. Moreover, serum level of immunoreactive insulin (IRI) (11 U ml −1 at fasting) and urinary excretion of C-peptide (108 g day −1 , reference range: 20-130) suggested insulin resistance, supported by results of insulin tolerance tests. With insulin therapy and cessation of IFN-␥, fasting blood glucose concentration returned to 6.2 mmol l −1 , and insulin therapy was discontinued. The injection of IFN-␥ may cause hyperglycaemia because of insulin resistance, rather than ␤-cell injury.

Treatment with IFN‐γ prevents insulin‐dependent PKB, p70S6k phosphorylation and protein synthesis in mouse C2C12 myogenic cells

“…The catabolic action of IFN‐γ on skeletal muscle, assessed on the basis of protein kinase activity, a myosin heavy chain content and the total protein/DNA ratio, was not supported by previous observations (Smith et al, 2007). In striking contrast, in the present study we found a marked modification of key intracellular insulin signalling pathways and protein synthesis in myogenic cells differentiated in the presence of IFN‐γ.…”

“…Such a discrepancy concerning the effect of IFN‐γ on muscle cell protein turnover could result from the experimental protocol used and/or from the differentiation state of the cells. In both studies, the action of IFN‐γ was examined in C2C12 myotubes; however, we investigated the protein synthesis and insulin signalling on the fifth day of differentiation after 5 days of cytokine treatment, whereas Smith et al (2007) described short‐term effects, with IFN‐γ treatment lasting a few hours (for assessment of the activity of signalling molecules) or 3 days (for assessment of differentiation parameters).…”

IL-6 and IGF-1 are Independent Prognostic Factors of Liver Steatosis and Non-Alcoholic Steatohepatitis in Morbidly Obese Patients

“…12 Obesity is characterized by a broad inflammatory response and many inflammatory mediators exhibit patterns of expression and/or impact insulin action that correlates with the progression of metabolic syndrome. [14][15][16][17][18] TNF-α and IL-6 expressions are enhanced in the adipose tissue in human obesity and IR. [14][15][16][17][18] TNF-α and IL-6 expressions are enhanced in the adipose tissue in human obesity and IR.…”

Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants

“…Two representative examples are the diabetogenic effect of steroids [5] and the cyclosporine-induced inhibition of insulin production by b cells [6]. However, recent findings indicate that certain proinflammatory cytokines are capable of interfering with insulin-sensitive glucose uptake and induce insulin resistance [7], as well as affecting adipose tissue metabolism [8] and modulating blood pressure [9]. Intriguingly, a member of "adipocytokine" family, TNF-a is over-expressed in the adipose tissue of obese humans [10], and contributes to insulin resistance by up-regulating free fatty acid secretion, inhibiting insulin signaling in adipocytes, and down-regulating glucose transporters [11].…”