Adiponectin Is Functionally Active in Human Islets but Does Not Affect Insulin Secretory Function or β-Cell Lipoapoptosis

Staiger, K.; Stefan, Norbert; Staiger, Harald; Brendel, Mathias D.; Brandhorst, Daniel; Bretzel, Reinhard G.; Machicao, Fausto; Kellerer, Monika; Stümvoll, Michael; Fritsche, Andreas; Häring, Hans Ulrich

doi:10.1210/jc.2005-0467

Cited by 75 publications

(77 citation statements)

References 32 publications

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“…A previous study showed that while adiponectin decreased glucose/forskolin-induced insulin secretion, it reversed NEFA-induced inhibition of insulin secretion [13]. Another group reported that adiponectin had no effect on either basal or stimulated insulin secretion from human islets [38]. Winzell et al [39] reported that adiponectin decreases insulin secretion from the pancreatic islets of insulin-resistant mice at a 2.8 mmol/l glucose, but stimulates insulin secretion at 16.7 mmol/l glucose.…”

Section: Discussionmentioning

confidence: 98%

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

et al. 2008

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Aims/hypothesis A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin may be involved in the regulation of insulin secretion in vivo and in vitro. Methods The effect of adiponectin on insulin secretion was measured in vitro and in vivo, along with the effects of adiponectin on ATP generation, membrane potentials, Ca 2+ currents, cytosolic calcium concentration and state of 5′-AMP-activated protein kinase (AMPK). In addition, insulin granule transport was measured by membrane capacitance and total internal reflection fluorescence (TIRF) analysis.Results Adiponectin significantly stimulated insulin secretion from pancreatic islets to approximately 2.3-fold the baseline value in the presence of a glucose concentration of 5.6 mmol/l. Although adiponectin had no effect on ATP generation, membrane potentials, Ca 2+ currents, cytosolic calcium concentrations or activation status of AMPK, it caused a significant increase of membrane capacitance to approximately 2.3-fold the baseline value. TIRF analysis revealed that adiponectin induced a significant increase in the number of fusion events in mouse pancreatic beta cells under 5.6 mmol/l glucose loading, without affecting the status of previously docked granules. Moreover, intravenous injection of adiponectin significantly increased insulin secretion to approximately 1.6-fold of baseline in C57BL/6 mice. Diabetologia (2008) Conclusions/interpretation The above results indicate that adiponectin induces insulin secretion in vitro and in vivo.

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Section: Discussionmentioning

confidence: 98%

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

et al. 2008

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“…Finally, a growing body of literature has recently queried a link between adiponectin and beta cell function, although conclusive resolution of this question remains elusive owing to some conflicting observations in this asyet modest literature. Specifically, adiponectin receptors are expressed on beta cells [28,29], although in vitro studies have reported conflicting findings with respect to the ability of adiponectin to stimulate insulin secretion [29,30]. In humans, low circulating adiponectin concentration has been associated with beta cell dysfunction in some [21,[31][32][33][34], but not all [29,35], studies, possibly because of differences in: (1) the methods used to evaluate beta cell function; (2) the populations under study; and (3) their sample sizes.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, adiponectin receptors are expressed on beta cells [28,29], although in vitro studies have reported conflicting findings with respect to the ability of adiponectin to stimulate insulin secretion [29,30]. In humans, low circulating adiponectin concentration has been associated with beta cell dysfunction in some [21,[31][32][33][34], but not all [29,35], studies, possibly because of differences in: (1) the methods used to evaluate beta cell function; (2) the populations under study; and (3) their sample sizes. Of note, the only two previous studies examining this question during pregnancy have indeed linked hypoadiponectinaemia and beta cell dysfunction in women with and without GDM [21,31].…”

Section: Discussionmentioning

confidence: 99%

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

Retnakaran

Qi²,

Connelly

et al. 2009

Diabetologia

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Aims/hypothesis The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterised. Thus, we sought to determine whether adiponectin, leptin and CRP levels during pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes.Methods Metabolic characterisation, including oral glucose tolerance testing, was undertaken in 487 women during pregnancy and at 3 months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance and 259 with normal glucose tolerance. Results Adiponectin levels were lowest (p<0.0001) and CRP levels highest (p=0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p = 0.4483). Adiponectin (r = 0.41, p < 0.0001), leptin (r= −0.36, p <0.0001) and CRP (r = −0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS OGTT ]). Intriguingly, adiponectin levels were also related to postpartum beta cell function (insulinogenic index/HOMA of insulin resistance; r=0.16, p=0.0009). Indeed, on multiple linear regression analyses, adiponectin levels during pregnancy independently predicted both postpartum insulin sensitivity (t=3.97, p<0.0001) and beta cell function (t=2.37, p=0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t=−3.01, p=0.0027). Conclusions/interpretation Hypoadiponectinaemia during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

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“…Adiponectin was recently reported to have insulin-sensitizing, anti-atherogenic and -inflammatory actions but no effect on insulin secretion (23). Adipsin is secreted by adipocytes, and adipsin release at the cell surface is stimulated by insulin.…”

Section: Discussionmentioning

confidence: 99%

Suppression of MafA mRNA with siRNA prevents adipose cell differentiation in 3T3-L1 cells

Tsuchiya

Maeda²,

Suzuki³

et al. 2009

Int J Mol Med

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Abstract.One of the large Mafs, MafA protein, is a strong transactivator of insulin in pancreatic ß cells. Mafs are also known to play important roles in a variety of developmental and differentiation processes in many organs and tissues. Adipocytes are highly involved in insulin actions and glucose and lipid metabolism, and their proliferation and differentiation is regulated by coordination of several signal transduction and transcriptional factors, including members of the Maf family. To explore the role of MafA in adipocytes, we modified the MafA mRNA level in cultured adipocytes by the RNA interference technique and analyzed the resulting morphological changes and changes in expression of related genes. MafA siRNA was transfected into 3T3-L1 adipocytes. Expression of MafA was confirmed by real-time PCR and Western blotting. Expression of adipocytokines and transcriptional factors was also measured by real-time PCR. Cells were examined for morphological changes and lipid accumulation by microscopy. The MafA expression level in the MafA-siRNA-transfected pre-adipocytes was reduced by ~30% on day 0 pre-induction and by ~70% on day 3 post-induction, in comparison with stop-siRNA-transfected cells. Cell growth and lipid droplet accumulation were prevented by MafA mRNA suppression, and peroxisome proliferator-activated receptor (PPAR) Á2 and CCAAT/enhancerbinding proteins (C/EBP)·, both of which are transcriptional factors essential for adipocyte differentiation, were downregulated. Expression of the genes encoding the adipocytokines, adiponectin and adipsin was also suppressed. The results suggested a possible role of the transcriptional factor MafA in regulation of adipocyte function and differentiation. IntroductionThe large Maf proteins are a family of transcription factors characterized by a typical bZip structure, which is a motif for protein dimerization and DNA binding, and they were reported to regulate several distinct developmental processes, cell differentiation, and the establishment of cell functions (1-3). One of the large Mafs, MafA protein, is a strong transactivator of insulin in pancreatic ß cells (4,5), and there are many reports that MafA transcription factor contributes to ß cell function and differentiation (6-9). One study demonstrated that loss of MafA protein causes a decrease in insulin gene expression in glucotoxic ß cells (10), and another study showed a marked reduction of insulin transcription in MafA-deficient mice, even though the insulin content of ß cells was not significantly reduced (11).On the other hand, it is well known that the Mafs play important roles in a variety of developmental and differentiation processes in many organs, tissues, and cells, including the pancreas (12), lens (13), myeloma cells (14), and cartilage (15). Adipocytes are closely related to insulin action and glucose as well as lipid metabolism, and are candidates for Maf-related cells (16). Their differentiation and proliferation is regulated by coordination of several signal transduction and transcript...

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Adiponectin Is Functionally Active in Human Islets but Does Not Affect Insulin Secretory Function or β-Cell Lipoapoptosis

Cited by 75 publications

References 32 publications

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

Suppression of MafA mRNA with siRNA prevents adipose cell differentiation in 3T3-L1 cells

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