Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus

Kratzsch, Jürgen; Deimel, A; Galler, Angela; Kapellen, Thomas; Klinghammer, A; Kieß, Wieland

doi:10.1530/eje.0.1510475

Cited by 28 publications

(25 citation statements)

References 40 publications

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“…PKC can induce A disintegrin and metalloprotease (ADAM) 17 (22), which is able to shed the extracellular domain of cytokine-like hormone receptors, such as the growth hormone-receptor and the OB-R, leading to increased levels of the soluble receptor. The fact that deficiency of substrates for the energy supply, such as lack of intracellular glucose in T1DM, leads to increased levels of circulating sOB-R is in agreement with previous data showing the same effect in conditions with weight loss, malnutrition, insulin treatment of T1DM with poor glycemic control, or nephrotic syndrome (14,(23)(24)(25)(26). Furthermore, our data suggest that age, height-SDS, and parameters of metabolic decompensation have the strongest power for the prediction of sOB-R variance.…”

Section: Discussionsupporting

confidence: 92%

“…Type 1 diabetes mellitus (T1DM) may lead to increased serum levels of the sOB-R, so far, by an unknown mechanism. The observed molar excess of sOB-R may contribute to leptin insensitivity in these patients, which supports weight gain and a decrease in energy consumption in catabolic conditions like the newly diagnosed T1DM (14). However, the detailed role of the leptin axis in pathogenesis of T1DM remains unclear.…”

Section: Introductionmentioning

confidence: 73%

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Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Kratzsch

Knerr²,

Galler³

et al. 2006

eur j endocrinol

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Objective: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. Materials and methods: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (nZ25), during the first 18 h (meanGS.D. 11.1G 4.3 h, nZ16) and 92 h (47.5G22.5 h; nZ14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. Results: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P!0.05). In contrast, leptin levels were significantly lower (P!0.05) before insulin therapy. The correlation between sOB-R and blood glucose (rZ0.49; P!0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (rZK0.72), base excess (rZK0.70), and bicarbonate (rZK0.69) (P!0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P!0.001), age 16.4% (P!0.05), and height SDS 13.9% (P!0.01) of the sOB-R variance. Conclusions: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.European Journal of Endocrinology 155 609-614

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 73%

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Kratzsch

Knerr²,

Galler³

et al. 2006

eur j endocrinol

Self Cite

View full text Add to dashboard Cite

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“…Accumulating data favor the view that elevated levels of sOBR is a beneficial biomarker for enhanced leptin sensitivity, which is generally associated with energy surplus condition as in obesity. Worth to mention is that increased plasma sOBR levels are also frequently associated with energy-deficient conditions, as is the case for fasting (Chan et al 2002), food deprivation (Cohen et al 2005), type 1 diabetes (Kratzsch et al 2004, eating disorders such as anorexia nervosa and bulimia nervosa (Monteleone et al 2002) or catabolic states as in nephritic syndrome (Schroth et al 2003) and severe malnutrition (Stein et al 2006). In such conditions, the increased sOBR levels are generally regarded as a compensatory mechanism by which leptin action is antagonized; hence, food intake is promoted and energy consumptions decreased, so as to replenish the body's energy shortage.…”

Section: Discussionmentioning

confidence: 99%

Metformin increases hepatic leptin receptor and decreases steatosis in mice

Tang

Xiang

et al. 2016

Journal of Endocrinology

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In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying these effects are still incompletely understood. Emerging evidence suggest metformin as leptin sensitizer to mediate the weight-loss effect in the brain. In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5 months. Afterward, mice were treated with metformin (50 mg/kg or 200 mg/kg) for 15 days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dosedependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis.

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“…Excess adiposity, in general a proinflammatory state, [101][102][103] is associated with both microvascular and macrovascular complications in T1DM. 104,105 Levels of the adipokine leptin and its associated leptin receptor, which are involved in signaling satiety in the brain, are also increased in T1DM, 106 and leptin may be proinflammatory. 107 Additionally, the increased CD40 ligand expression and platelet-monocyte aggregation in T1DM may contribute to the accelerated rate of atherogenesis in these patients.…”

Section: Inflammation and T1dmmentioning

confidence: 99%