PANDER KO mice on high-fat diet are glucose intolerant yet resistant to fasting hyperglycemia and hyperinsulinemia

Robert-Cooperman, Claudia E.; Wilson, Camella G.; Burkhardt, Brant R.

doi:10.1016/j.febslet.2011.04.005

Cited by 16 publications

(21 citation statements)

References 19 publications

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“…Wilson et al . also reported that circulating PANDER is elevated in obese C57BL/6 mice . The relationship between PANDER and insulin in β cells may be similar to that between amylin (islet amyloid polypeptide, a 37‐amino acid peptide) and insulin.…”

Section: Fam3b (Pander) and Nafldmentioning

confidence: 80%

“…Immunohistochemical staining and confocal microscopy assays further revealed that FAM3B protein is specifically localized in the islets within the pancreas . Therefore, FAM3B is also called PANDER in subsequent studies . Human and mouse PANDER proteins are composed of 235 amino acid residues with a 29‐amino acid N‐terminal signal peptide and share high‐sequence homology among species.…”

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

“…Although PANDER‐deficient mice exhibit glucose intolerance because of impaired insulin secretion from islet β cells, they also show reduced hepatic glucose production (HGP) because of enhanced insulin sensitivity, as assessed by a hyperinsulinemic‐euglycemic clamp assay . PANDER‐deficient mice are protected against HFD‐induced fasting hyperglycemia via reducing HGP, mainly resulting from decreased expression of gluconeogenic genes phosphoenolpyruvate carboxykinase ( PEPCK ) and glucose‐6‐phosphatase ( G6Pase ) . In contrast, adenovirus‐mediated overexpression of PANDER in the liver of C57BL/6 mice results in hyperglycemia and hyperinsulinemia, which is associated with increased gluconeogenesis in the liver via the upregulation of PEPCK and G6Pase .…”

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

“…17,18 Therefore, FAM3B is also called PANDER in subsequent studies. [18][19][20][21][22][23][24][25][26][28][29][30] Human and mouse PANDER proteins are composed of 235 amino acid residues with a 29-amino acid N-terminal signal peptide and share high-sequence homology among species.…”

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

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Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease

Yang

Guan

2013

J of Gastro and Hepatol

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Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as well as liver-related morbidity and mortality worldwide. NAFLD is also associated with increased risk of cardiovascular diseases, hyperlipidemia, and type2 diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members designated FAM3A, FAM3B, FAM3C, and FAM3D, respectively. Increasing evidence suggests that the FAM3 gene family members are involved in the pathogenesis of NAFLD. In particular, FAM3B, also called pancreatic-derived factor, is an important regulator of glucose and lipid metabolism. In obesity status, increased expression and secretion of FAM3B in pancreatic islets and liver may induce lipid accumulation in the liver via the induction of hepatic insulin resistance and lipogenesis. FAM3A and FAM3D may also participate in the regulation of lipid and energy metabolism. In this brief review, we discussed the latest findings regarding the role of FAM3 gene family members, in particular FAM3B, in the pathogenesis of NAFLD.

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Section: Fam3b (Pander) and Nafldmentioning

confidence: 80%

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

Section: Fam3b (Pander) and Nafldmentioning

confidence: 99%

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Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease

Yang

Guan

2013

J of Gastro and Hepatol

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“…Conversely, while there were no differences in fasted glucose levels in the PANKO mice on normal chow diet, after HFD feeding for 10 weeks, glucose levels following a 24-or 48-h fast were significantly lower in PANKO mice [17,22] and more similar to their normal diet (ND, 16.7% fat by calories) fed counterparts. This suggests that loss of PANDER may protect mice on a HFD from developing gross fasting hyperglycemia and that PANDER may be an important target for inhibiting HFD-induced fasting hyperglycemia.…”

Section: Pander Lipids and Hyperglycemiamentioning

confidence: 89%

PANcreatic-DERived factor: Novel hormone PANDERing to glucose regulation

2011

Self Cite

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Pancreatic-Derived Factor (PANDER, FAM3B) is a member of the FAM3 family of cytokine molecules that were initially described in 2002. PANDER expression is primarily localized to the endocrine pancreas and is secreted from both pancreatic α and β-cells. Initial characterization of PANDER revealed a potential role in pancreatic islet apoptosis. However, recent animal models have indicated PANDER functions as a hormone by regulating glucose levels via interaction with both the liver and the endocrine pancreas. An understanding of the function of PANDER can further the insight into the mechanisms of glucose regulation and potentially provide additional therapeutic targets for the treatment of diabetes. This review details the supporting data demonstrating PANDER has a biological function in glycemic regulation.

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FAM3A activates PI3K p110α/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis

et al. 2014

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FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found a marked reduction of FAM3A expression in the livers of db/db and high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression of FAM3A markedly attenuated hyperglycemia, insulin resistance, and fatty liver with increased Akt (pAkt) signaling and repressed gluconeogenesis and lipogenesis in the livers of those mice. In contrast, small interfering RNA (siRNA)-mediated knockdown of hepatic FAM3A resulted in hyperglycemia with reduced pAkt levels and increased gluconeogenesis and lipogenesis in the livers of C57BL/6 mice. In vitro study revealed that FAM3A was mainly localized in the mitochondria, where it increases adenosine triphosphate (ATP) production and secretion in cultured hepatocytes. FAM3A activated Akt through the p110a catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca 21 levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM). Conclusion: FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PI3K-Akt signaling pathway by way of a Ca 21 /CaM-dependent mechanism. Up-regulating hepatic FAM3A expression may represent an attractive means for the treatment of insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). (HEPATOLOGY 2014;59:1779-1790 T ype 2 diabetes has become one of the most prevalent and debilitating chronic diseases, with a global prevalence 6.4%, affecting about 285 million adults in the year 2010.1 Hepatic insulin resistance and fatty liver play a crucial role in the development and progression of type 2 diabetes. Liver is the key tissue regulating release of glucose into circulation during the fasting state, and hepatic insulin resistance is a decisive factor causing fasting hyperglycemia and type 2 diabetes. The liver is also one of the major organs regulating triglyceride (TG) and cholesterol (CHO) metabolism.2 Hepatic insulin resistance is mainly described as the failure of insulin to repress the expression of gluconeogenic genes through the PI3K/ Akt signaling pathway and is closely associated with the dysregulation of glucose and lipid metabolism in the liver.2 Although the underlying mechanisms remain largely unknown, increasing evidence points to

show abstract

PANDER KO mice on high-fat diet are glucose intolerant yet resistant to fasting hyperglycemia and hyperinsulinemia

Cited by 16 publications

References 19 publications

Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease

Family with sequence similarity 3 gene family and nonalcoholic fatty liver disease

PANcreatic-DERived factor: Novel hormone PANDERing to glucose regulation

FAM3A activates PI3K p110α/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis

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