The diabetic phenotype caused by the deletion of insulin receptor substrate-2 (Irs-2) in mice displays a sexual dimorphism. Whereas the majority of male Irs-2(-/-) mice are overtly diabetic by 12 weeks of age, female Irs-2(-/-) animals develop mild obesity and progress less rapidly to diabetes. Here we investigated β-cell function and lipolysis as potential explanations for the gender-related differences in this model. Glucose-stimulated insulin secretion was enhanced in islets from male null mice as compared to male WT whereas this response in female Irs-2(-/-) islets was identical to that of female controls. The ability of α(2)-adrenoceptor (α(2)-AR) agonists to inhibit insulin secretion was attenuated in male Irs2 null mice. Consistent with this, the expression of the α(2A)-AR was reduced in male Irs-2(-/-) islets. The response of male Irs-2(-/-) islets to forskolin was enhanced, owing to increased production of cAMP. Basal lipolysis was increased in male Irs-2(-/-) but decreased in female Irs-2(-/-) mice, concordant with the observation that adipose tissue is sparse in males whereas female Irs2 null mice are mildly obese. Adipocytes from both male and female Irs-2(-/-) were resistant to the anti-lipolytic effects of insulin but female Irs-2(-/-) fat cells were additionally resistant to the catabolic effects of beta-adrenergic agonists. This catecholamine resistance was associated with impaired generation of cAMP. Consequently, targets of cAMP-dependent protein kinase (PKA) which mediate lipolysis were not phosphorylated in adipose tissue of female Irs-2(-/-) mice. Our findings suggest that IRS-2 deficiency in mice alters the expression and/or sensitivity of components of adrenergic signaling.

<b><i>Introduction:</i></b> Macular pigment optical density (MPOD) plays a pivotal role in maintaining macular structure and functioning. Research shows that daily consumption of lutein reduces the risk of eye diseases such as age-related macular degeneration. <b><i>Objective:</i></b> This study analyzes the influence of a supplementation containing lutein and antioxidant vitamins either with or without docosahexaenoic acid (DHA), with the main objective of identifying MPOD changes in both eyes at the end of the follow-up using the Visucam®retinograph. The secondary end point was to determine variation in the lutein and DHA levels in plasma and red blood cell membranes (RBCMs), respectively. <b><i>Methods:</i></b> One hundred healthy participants (200 eyes) aged 40–70 years (mean age 49.3 years, SEM = 13.7) were randomized in a 1:1 ratio to receive daily one of the following supplements for 3 months: lutein group (LT-G, <i>n</i> = 49) and lutein plus DHA group (LT/DHA-G, <i>n</i> = 51). The MPOD was measured at baseline and end of the follow-up by retinography (Visucam®retinograph). Lutein in plasma was determined by HPLC, and DHA in RBC membranes was analyzed by gas chromatograph/mass spectrometer. <b><i>Results:</i></b> From baseline, MPOD showed significantly higher values in the LT/DHA-G than in the LT-G at the end of the study (<i>p</i> &#x3c; 0.0001). Significantly higher lutein in plasma (<i>p</i> &#x3c; 0.0001) and DHA (<i>p</i> &#x3c; 0.0001) levels in the RBC membrane were seen in the LT/DHA-G than in the LT-G at the 3-month follow-up. <b><i>Conclusion:</i></b> Lutein supplementation improves MPOD in healthy subjects from a Mediterranean population being significantly increased in the presence of DHA. Therefore, our findings highlight the relevance of the adjunctive role of DHA for better lutein availability.