OBJECTIVEImpaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.RESEARCH DESIGN AND METHODSSerum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort.RESULTSIn the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.CONCLUSIONSThese findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.
OBJECTIVE -Visfatin is a novel adipokine that is predominantly secreted by visceral adipose tissue. Accumulation of visceral adipose tissue is also associated with iron metabolism. Despite the coincidence of visfatin expression in iron-rich tissues, no study has investigated the possible interaction of visfatin with parameters of iron metabolism.RESEARCH DESIGN AND METHODS -We evaluated insulin sensitivity and parameters of iron metabolism in 95 men with normal glucose tolerance (NGT) and 43 men with altered glucose tolerance.RESULTS -Men with newly diagnosed type 2 diabetes had significantly increased serum visfatin in parallel with increased serum prohepcidin and serum ferritin compared with the other groups. In all subjects as a whole, circulating visfatin was not found to be significantly linked to insulin sensitivity (r ϭ 0.07, P ϭ 0.4) but was significantly associated with serum prohepcidin concentration (r ϭ 0.40, P Ͻ 0.0001). Obesity status and glucose tolerance status influenced the relationships among visfatin, insulin sensitivity, and parameters of iron metabolism. Among men with altered glucose tolerance, serum visfatin was strongly associated with serum prohepcidin (r ϭ 0.61, P Ͻ 0.0001) and serum soluble transferrin receptor (sTfR) (r ϭ Ϫ0.51, P Ͻ 0.0001). In nonobese subjects, sTfR (P ϭ 0.02) and prohepcidin (P ϭ 0.04) contributed independently to visfatin variance after controlling for age and BMI. When insulin sensitivity was added to the model, only the latter (P ϭ 0.006) contributed to 17% of visfatin variance. In obese men, however, only sTfR (P ϭ 0.04) contributed independently to visfatin variance in this latter model.CONCLUSIONS -Serum visfatin concentration is significantly associated with parameters of iron metabolism, especially in subjects with altered glucose tolerance. Diabetes Care 30:616 -621, 2007V isfatin, also known as pre--cell colony-enhancing factor (1), is a novel adipokine that is predominantly secreted by visceral adipose tissue (2), although controversy exists over the contribution of this fat depot to serum visfatin in humans (2,3). The protein exerts adipogenic effects in vitro and therefore is a good candidate to explain the accumulation of visceral adipose tissue that is associated with insulin resistance (2). Accumulation of visceral adipose tissue is also associated with iron metabolism. Serum ferritin is linked to centrally distributed body fatness. Studies in Norwegian (4) and Mexican-American men (5) demonstrated independent associations between serum ferritin concentrations and the waist-to-thigh ratio (4) or the waist-to-hip ratio (5). Serum ferritin concentration was also significantly associated with the computed tomographyestimated visceral fat area, hepatic fat content, and the degree of insulin resistance (6).The maximum level of visfatin mRNA was found in the liver tissue and the next highest amount was found in muscle tissue (1). These tissues are classically insulin sensitive but are also characterized as central in iron metabolism. High expression of ...
OBJECTIVE -The relationships between iron metabolism and type 2 diabetes are bidirectional: iron affects glucose metabolism and glucose metabolism impinges on several iron metabolic pathways. The mechanisms of these interactions depend on poorly known factors. We aimed to study the contribution of the serum soluble transferrin receptor (sTfR). RESEARCH DESIGN AND METHODS -Circulating sTfR was evaluated in 221 men(97 with normal glucose tolerance [NGT], 36 with impaired glucose tolerance, and 88 with type 2 diabetes). In a subset of these subjects, glucose tolerance (oral glucose tolerance test [OGTT]), minimal model-derived insulin sensitivity, and sTfR during the OGTT were also evaluated.RESULTS -Men with altered glucose tolerance showed significantly increased sTfR (9.4 Ϯ 4.4 vs. 8.2 Ϯ 2.6 g/ml, P ϭ 0.02) and higher serum ferritin than men with NGT. Serum sTfR was negatively associated with serum ferritin (r ϭ Ϫ0.16, P ϭ 0.02). sTfR correlated with several clinical and metabolic variables such as systolic blood pressure, glycated hemoglobin, and glucose and insulin values during OGTT. Insulin sensitivity was also negatively associated with sTfR in NGT and nonobese subjects. BMI (P ϭ 0.01), serum ferritin (P ϭ 0.025), and insulin sensitivity (P Ͻ 0.0001) contributed independently to 21% of sTfR variance. Serum sTfR concentration did not significantly change during the OGTT.CONCLUSIONS -Both insulin sensitivity and glucose tolerance status are significantly associated with serum sTfR concentrations, although insulin sensitivity predicts independently circulating sTfR, mainly in subjects with NGT. The implications of the interrelationships between iron and glucose metabolism should be investigated further. Diabetes Care 30:604 -608, 2007I nsulin is an anabolic hormone that stimulates the cellular uptake of many nutrients, including hexoses, amino acids, cations, and anions. In the steady state, iron circulates bound to transferrin and is taken up from the blood by a highaffinity specific transferrin receptor (TfR) (1). The TfR complex is internalized by endocytosis and released into a nonacidic cellular compartment, where it can be used in the synthesis of essential cellular components. Insulin is known to cause a rapid and marked stimulation of iron uptake by fat cells, redistributing TfRs from an intracellular membrane compartment to the cell surface (2). Insulin also induces iron transport and accumulation in hepatocytes by a similar mechanism (2) and is responsible for increased ferritin synthesis in cultured rat glioma cells (3). TfRs have been shown to colocalize with insulin-responsive glucose transporters and IGF-II receptors in the microsomal membranes of cultured adipocytes, suggesting that regulation of iron uptake by insulin parallels its effects on glucose transport (4).The synthesis of TfR and the iron storage protein ferritin is regulated reciprocally at the posttranscriptional level according to the cellular iron status (5). As a result of the externalization of TfR during the endocytic cycle, a s...
OBJECTIVES -Impaired lung function and inflammation have both attracted interest as potentially novel risk factors for glucose intolerance, insulin resistance, and type 2 diabetes. We hypothesized that circulating levels of surfactant protein (SP)-A, which reflects interstitial lung injury, could be associated with altered glucose tolerance and insulin resistance.RESEARCH DESIGN AND METHODS -Circulating SP-A concentration and metabolic variables (including insulin sensitivity by minimal model method, n ϭ 89) were measured in 164 nonsmoking men.RESULTS -Circulating SP-A concentration was significantly higher among patients with glucose intolerance and type 2 diabetes than in subjects with normal glucose tolerance, even after adjustment for BMI, age, and smoking status (ex/never). The most significant differences were found in overweight and obese subjects with altered glucose tolerance (n ϭ 59) who showed significantly increased serum SP-A concentrations (by a mean of 24%) compared with obese subjects with normal glucose tolerance (n ϭ 58) (log SP-A 1.54 Ϯ 0.13 vs. 1.44 Ϯ 0.13; P Ͻ 0.0001). Insulin sensitivity (P ϭ 0.003) contributed independently to 22% of SP-A variance among all subjects. In subjects with altered glucose tolerance, insulin sensitivity (P ϭ 0.01) and fasting triglycerides (P ϭ 0.02) contributed to 37% of SP-A variance. Controlling for serum creatinine or C-reactive protein in these models did not significantly change the results.CONCLUSIONS -Lung-derived SP-A protein was associated with altered glucose tolerance and insulin resistance in 164 nonsmoking men. Diabetes Care 31:958-963, 2008
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.