RETRACTED: Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation

Peng, Yi; Park, Ji Sun; Melton, Douglas A.

doi:10.1016/j.cell.2013.04.008

Cited by 453 publications

(609 citation statements)

References 57 publications

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“…Diminished insulin sensitivity induced by insulin receptor antagonists increases hepatic betatrophin expression in mouse models 1 and serum betatrophin concentrations are decreased in obesity and are negatively associated with insulin resistance 10. These results support the premise that betatrophin levels are regulated by insulin resistance and not by insulin deficiency per se .…”

Section: Discussionsupporting

confidence: 63%

“…1 identified a secreted protein, termed betatrophin, which links hepatic insulin resistance to β‐cell proliferation in mice. Betatrophin, also known as hepatocellular carcinoma‐associated protein TD26 2, refeeding‐induced fat and liver protein 3, lipasin 4 and angiopoietin‐like protein 8 5, is a potential stimulator of β‐cell mass expansion; however, according to the few available experimental study results, although betatrophin dramatically stimulates the proliferation of mouse β cells 1, its effects on the proliferation of human β cells are limited 6. The pathophysiological role and even metabolism of betatrophin are still unclear, and the relationship between betatrophin and human β‐cell function has yet to be addressed.…”

Section: Introductionmentioning

confidence: 99%

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Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

et al. 2015

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AimTo investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes.MethodsGlucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme‐linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C‐peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24‐h urine samples.ResultsPlasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C‐peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C‐peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C‐peptide concentration as independent factors associated with plasma betatrophin levels.ConclusionPlasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

et al. 2015

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“…In favour of the former, several factors have been described as protecting beta cells in animal models, such as hepatocyte growth factor, gastric inhibitory polypeptide (GIP), insulin-like growth factor 1 (IGF-1), and prolactin. In terms of evidence for the latter, glucagon-like peptide 1 (GLP-1), liver-derived factors [4] and betatrophin (also termed angiopoietin-like 8, RIFL or lipasin) [5] have been reported to increase beta cell proliferation. While expansion of existing beta cells in vivo has mostly been explored in rodents [6,7], limited data from obese or insulinresistant humans also indicate a potential for islet mass expansion.…”

Section: Introductionmentioning

confidence: 99%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

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Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

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“…Recently, Melton and his colleagues (13) reported that hepatic overexpression of ANGPTL8, which they called Betatrophin, promotes proliferation of pancreatic β-cells and increases insulin secretion. Thus, ANGPTL8 may also contribute to glucose homeostasis.…”

mentioning

confidence: 99%

Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis

Wang

Quagliarini²,

Gusarova

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

294

354

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Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8 −/− ) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8 −/− mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8 −/− mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.

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RETRACTED: Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation

Cited by 453 publications

References 57 publications

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis

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