Regulation of glucose and lipid homeostasis by adiponectin: Effects on hepatocytes, pancreatic β cells and adipocytes

Tao, Caroline; Sifuentes, Angelica; Holland, William L.

doi:10.1016/j.beem.2013.11.003

Cited by 109 publications

(81 citation statements)

References 126 publications

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“…The insulin sensitizing molecule adiponectin reduces ceramide levels and enhances S1P formation in the liver of mice. This change of the ceramide/S1P balance is connected with an improved insulin signaling [35]. In agreement, a modulation of the ceramide/S1P level is also visible in acid sphingomyelinase-deficient mice.…”

Section: Role Of S1p On Hepatic Insulin Resistancesupporting

confidence: 58%

Divergent Role of Sphingosine 1-Phosphate on Insulin Resistance

Fayyaz

Japtok

Kleuser

2014

Cell Physiol Biochem

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Insulin resistance is a complex metabolic disorder in which insulin-sensitive tissues fail to respond to the physiological action of insulin. There is a strong correlation of insulin resistance and the development of type 2 diabetes both reaching epidemic proportions. Dysfunctional lipid metabolism is a hallmark of insulin resistance and a risk factor for several cardiovascular and metabolic disorders. Numerous studies in humans and rodents have shown that insulin resistance is associated with elevations of non-esterified fatty acids (NEFA) in the plasma. Moreover, bioactive lipid intermediates such as diacylglycerol (DAG) and ceramides appear to accumulate in response to NEFA, which may interact with insulin signaling. However, recent work has also indicated that sphingosine 1-phosphate (S1P), a breakdown product of ceramide, modulate insulin signaling in different cell types. In this review, we summarize the current state of knowledge about S1P and insulin signaling in insulin sensitive cells. A specific focus is put on the action of S1P on hepatocytes, pancreatic β-cells and skeletal muscle cells. In particular, modulation of S1P-signaling can be considered as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.

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Section: Role Of S1p On Hepatic Insulin Resistancesupporting

confidence: 58%

Divergent Role of Sphingosine 1-Phosphate on Insulin Resistance

Fayyaz

Japtok

Kleuser

2014

Cell Physiol Biochem

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“…6) (28). As the literature shows, IGF-I has strong adipogenic and anti-inflammatory properties (21,24,30,32,66,70,75,80), as does adiponectin (14,47,63,68), whereas leptin is known to be proinflammatory and adipolytic (7,14,47). IL-6, another cytokine known to have proinflammmatory and adipolytic properties (34,40,42), was also consistently decreased following BAT transplants.…”

Section: Discussionmentioning

confidence: 94%

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Gunawardana

Piston

2015

American Journal of Physiology-Endocrinology and Metabolism

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Gunawardana SC, Piston DW. Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant. Am J Physiol Endocrinol Metab 308: E1043-E1055, 2015. First published April 21, 2015; doi:10.1152/ajpendo.00570.2014.-Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and longlasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulinlike growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium. type 1 diabetes; brown adipose tissue; insulin independent; transplantation; insulin-like growth factor I TYPE 1 DIABETES (T1D) is characterized by autoimmune-mediated destruction of pancreatic ␤-cells, resulting in absolute deficiency of insulin and loss of glycemic control. Treatments for T1D, despite having been refined over many years, are geared mainly toward replacing insulin, which involves numerous risks and limitations. Direct insulin replacement via daily injections or insulin pump does not cure the disease and requires life-long repeated administration. In addition to the inconvenience, direct insulin therapy requires careful monitoring of dosage and blood glucose levels and can lead to potentially fatal hypoglycemic episodes. Pancreas transplantation, the only available treatment with a good chance of long-term insulin independence, requires invasive surgery and life-long immunosuppressive therapy. Islet transplantation, although less invasive, is limited by the availability of donor tissue and the need for immunosuppression, and patients often return to insulin dependence in the long...

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“…Sphingolipids, particularly sphingomyelins (SM), are ceramide precursors and usually colocalize with cholesterol on cell membranes and LDL surface (21). Evidence suggests that ceramide concentrations are associated with insulin resistance (12,21,46). The ratio of kynurenine to tryptophan levels (Kyn/Trp), an increasingly recognized marker of inflammation and metabolic alterations, has been shown to be high in adult overweight or obese individuals (24,53), and also appears to be related to waist circumference independent of age (24).…”

mentioning

confidence: 99%

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

Boulet

Chevrier

Grenier-Larouche

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

108

105

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profiling of obese individuals revealed altered concentrations of many metabolites, especially branched-chain amino acids (BCAA), possibly linked to altered adipose tissue BCAA catabolism. We tested the hypothesis that some features of this metabolite signature relate closely to visceral obesity and concomitant alterations in cardiometabolic risk factors. We also postulated that alterations in BCAA-catabolizing enzymes are predominant in visceral adipose tissue. Fifty-nine women (BMI 20 -41 kg/m 2 ) undergoing gynecologic surgery were recruited and characterized for overall and regional adiposity, blood metabolite levels using targeted metabolomics, and cardiometabolic risk factors. Adipose samples (visceral and subcutaneous) were obtained and used for gene expression and Western blot analyses. Obese women had significantly higher circulating BCAA and kynurenine/tryptophan (Kyn/Trp) ratio than lean or overweight women (P Ͻ 0.01). Principal component analysis confirmed that factors related to AA and the Kyn/Trp ratio were positively associated with BMI, fat mass, visceral or subcutaneous adipose tissue area, and subcutaneous adipocyte size (P Յ 0.05). AA-related factor was positively associated with HOMA-IR (P Յ 0.01). Factors reflecting glycerophospholipids and sphingolipids levels were mostly associated with altered blood lipid concentrations (P Յ 0.05). Glutamate level was the strongest independent predictor of visceral adipose tissue area (r ϭ 0.46, P Ͻ 0.001). Obese women had lower expression and protein levels of BCAA-catabolizing enzymes in visceral adipose tissue than overweight or lean women (P Յ 0.05). We conclude that among metabolites altered in obesity plasma concentrations of BCAA and the Kyn/Trp ratio are closely related to increased adiposity. Alterations in expression and protein levels of BCAA-catabolizing enzymes are predominant in visceral adipose tissue.

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Regulation of glucose and lipid homeostasis by adiponectin: Effects on hepatocytes, pancreatic β cells and adipocytes

Cited by 109 publications

References 126 publications

Divergent Role of Sphingosine 1-Phosphate on Insulin Resistance

Divergent Role of Sphingosine 1-Phosphate on Insulin Resistance

Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

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