Serum Preadipocyte Factor-1 Concentrations in Females with Obesity and Type 2 Diabetes Mellitus: The Influence of Very Low Calorie Diet, Acute Hyperinsulinemia, and Fenofibrate Treatment

Kaválková, Petra; Toušková, Věra; Roubíček, Tomáš; Trachta, Pavel; Urbanová, Marie; Drápalová, J.; Haluzíková, D; Mráz, Miloš; Novák, Daniel; Matoulek, Martin; Lacinová, Z; Haluzı́k, Martin

doi:10.1055/s-0033-1353210

Cited by 18 publications

(22 citation statements)

References 17 publications

(25 reference statements)

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“…In contrast to our findings in pregnant subjects, an association between Pref-1 and markers of impaired glucose metabolism has been demonstrated in non-pregnant populations. Here, Kavalkova and coworkers demonstrate convincingly that serum Pref-1 concentrations are significantly higher in patients with T2DM as compared to controls [14]. Furthermore, circulating Pref-1 concentrations correlate positively with markers of insulin resistance including FI and HOMA-IR [14].…”

Section: Discussionmentioning

confidence: 59%

Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

et al. 2015

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Section: Discussionmentioning

confidence: 59%

Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

et al. 2015

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“…The current findings provide a mechanistic explanation for the observed association between increased levels of DLK1 and impaired insulin sensitivity in diabetic mice (21) and rats (20), in obese patients (46), and in patients with type 2 diabetes (36). Although our studies are conducted in murine models, these findings may be relevant to normal human physiology.…”

Section: Discussionmentioning

confidence: 68%

“…DLK1 has already been implicated in many aspects of energy metabolism, starting with its role as an inhibitor of adipogenesis in vitro and in vivo (35) and its association with insulin resistance in both rodents and humans (19,20,36). The current study uncovers a new mechanism by which DLK1 links bone and energy metabolism.…”

Section: Discussionmentioning

confidence: 73%

“…Additionally, the antiresorptive therapy did not affect the risk for developing diabetes in three randomized placebo-controlled trials in postmenopausal women (48). On the other hand, the association between serum increased sDLK1 and the insulin resistance phenotype has been reported in rodent (20,21) and human studies (46) as well as in patients with type 2 diabetes (36,49). Thus, follow-up studies are needed to corroborate the relevance of changes in serum sDLK1 to Glu-OCN regulation of glucose metabolism in humans.…”

Section: Discussionmentioning

confidence: 94%

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DLK1 Regulates Whole-Body Glucose Metabolism: A Negative Feedback Regulation of the Osteocalcin-Insulin Loop

et al. 2015

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The endocrine role of the skeleton in regulating energy metabolism is supported by a feed-forward loop between circulating osteoblast (OB)-derived undercarboxylated osteocalcin (Glu-OCN) and pancreatic b-cell insulin; in turn, insulin favors osteocalcin (OCN) bioactivity. These data suggest the existence of a negative regulation of this cross talk between OCN and insulin. Recently, we identified delta like-1 (DLK1) as an endocrine regulator of bone turnover. Because DLK1 is colocalized with insulin in pancreatic b-cells, we examined the role of DLK1 in insulin signaling in OBs and energy metabolism. We show that Glu-OCN specifically stimulates Dlk1 expression by the pancreas. Conversely, Dlk1-deficient (Dlk1 2/2 ) mice exhibited increased circulating Glu-OCN levels and increased insulin sensitivity, whereas mice overexpressing Dlk1 in OB displayed reduced insulin secretion and sensitivity due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1 2/2 mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic b-cells acts as a negative feedback mechanism to counteract the stimulatory effects of insulin on OB production of Glu-OCN, a potential mechanism preventing OCN-induced hypoglycemia.A growing body of work indicates that bone is an endocrine organ that regulates glucose metabolism through, in part, the hormone osteocalcin (OCN). OCN signals in b-cells through its bona fide receptor Gprotein-coupled receptor (Gprc6a) to increase b-cell proliferation and insulin secretion and acts on peripheral tissues to increase energy expenditure (1-3). In turn, insulin signaling in osteoblasts (OBs) stimulates the activation of OCN by promoting its decarboxylation (Glu-OCN) through the bone resorption arm of bone remodeling (1,4). The physiological relevance of these findings have been supported through studies demonstrating skeleton as a site of insulin resistance in mice fed a high-fat diet (5). Moreover, patients with a dominant negative mutation in Gprc6a show evidence of glucose intolerance (3). In all likelihood, the Glu-OCN-insulin feed-forward loop must be under a negative regulation to protect from hypoglycemia. Soluble factors responsible for this regulation have not yet been identified despite the demonstrated ability of transcription factors activating transcription factor 4 (ATF4) and forkhead box protein O1 (FoxO1) to regulate glucose metabolism through a negative regulation of OCN bioavailability (6,7). Delta like-1 (DLK1), also known as preadipocyte factor-1 (Pref-1), is a transmembrane protein belonging to the Notch/serrate/delta family (8,9). The full ectodomain of DLK1 is proteolytically cleaved to generate a soluble active protein named fetal antigen-1 (FA1), which is secreted by endocrine cells of pancreas, ovary, Leydig cells of the testis, adrenal glands, and pituitary gland (10). DLK1 has

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“…Его концентрация в крови, по отрывочным данным, при ожирении ме-няется незначительно, но возрастает при сахарном диабете 2 типа (СД2) и снижается под влиянием низ-кокалорийной диеты [18], а исследования в области онкологии связывают этот пептид с влиянием на про-лиферацию и с попытками описания характеристик некоторых нейроэндокринных опухолей. Ирисин счи-тается миокином -пептидом, продуцируемым мио-цитами, но способным, в то же время, стимулировать «побурение» белой жировой ткани и экспрессию мар-кера бурого жира UCP1 (с последним мнением, правда, согласны не все).…”

Section: результаты и обсуждениеunclassified

Adipokines, myokines and cytokines in endometrial cancer patients: relations to obesity phenotype of excessive body mass and features of the tumor

2017

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Aim. To study serum content of a number of known adipokines, myokines and cytokines and compare obtained data with overweight phenotype and characteristics of tumor in untreated patients with endometrial cancer (EC) Materials and methods. The study included 88 patients with a mean age 60.080.67 years and a mean body mass index (BMI) 32.900.83. Patients were subjected to anthropometry and analysis of laboratory parameters, including serum level of leptin, adiponectin, omentin, prefilin (Pref-1), myostatin, irisin, IL-6 as well as insulinemia and insulin resistance index (HOMA-IR). On the basis of combination of anthropometric and laboratory data patients with overweight (BMI 25.0) were subdivided into the groups with "standard" (S) and conditionally "metabolically healthy" (MH) phenotype. Results. Levels of leptin, insulin and adiponectin in the serum of patients with EC are associated with BMI value and demonstrate significant differences between S and MH groups. Levels of prefilin, myostatin, and IL-6 are not associated with an increase in BMI, but are also different in patients with S and MH phenotype of overweight.For levels oа irisin, omentin, and TNF-alphathere is no peculiar dependence both, the BMI, and of belonging to a group with S or MH phenotype. Omentin level in the serum is associated with less favorable tumor differentiation (MH group), while IL-6 level with a more advanced stage of the tumor (all patients and group S). Conclusion. Adipokines, myokines and cytokines circulating in blood of EC patients vary in their connections with BMI or with "standard" or "metabolically healthy" phenotype of its excess. They vary also in relation to EC features, which in sum may have practical importance.

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Serum Preadipocyte Factor-1 Concentrations in Females with Obesity and Type 2 Diabetes Mellitus: The Influence of Very Low Calorie Diet, Acute Hyperinsulinemia, and Fenofibrate Treatment

Cited by 18 publications

References 17 publications

Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

DLK1 Regulates Whole-Body Glucose Metabolism: A Negative Feedback Regulation of the Osteocalcin-Insulin Loop

Adipokines, myokines and cytokines in endometrial cancer patients: relations to obesity phenotype of excessive body mass and features of the tumor

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