Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States

Ouaamari, Abdelfattah El; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit

doi:10.1016/j.celrep.2013.03.021

Cited by 16 publications

(24 citation statements)

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“…Although we did not investigated in detail the mechanisms behind this phenotype, one attractive hypothesis is that deletion of miR-21 / miR-21* in hepatocytes triggers a crosstalk between the liver and other peripheral organs such as the adipose tissue, muscle or pancreas. Such a crosstalk between liver and pancreas, mediated by liver-derived soluble factors, has been recently reported in mice having a liver-specific deletion of the insulin receptor66 or a liver-specific deletion of PTEN 37. In this regard, it is interesting to note that circulating levels of miR-21 are increased in human patients with NAFLD43 which may potentially impact the adipose tissue physiology.…”

Section: Discussionmentioning

confidence: 82%

Stress-activatedmiR-21/miR-21*in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption

Calo

Ramadori

Sobolewski

et al. 2016

Gut

104

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Michelangelo (2016). Stress-activatedmiR-21/miR-21*in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption. Gut:gutjnl-2015-310822. DOI: https://doi.org/10.1136/gutjnl-2015 Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption. How might it impact on clinical practice in the foreseeable future? Nicolas

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Section: Discussionmentioning

confidence: 82%

Stress-activatedmiR-21/miR-21*in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption

Calo

Ramadori

Sobolewski

et al. 2016

Gut

104

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“…In a series of elegant studies, the Kulkarni group determined that the enhanced b-cell replication is due to a liver-derived factor found in the systemic circulation (94). This circulating factor derived from mouse hepatocytes was even able to stimulate human b-cell replication ex vivo; however, the exact factor was not determined.…”

Section: Liver-derived Circulating Factors In Insulin Resistancementioning

confidence: 98%

Pancreatic β-Cell Proliferation in Obesity

Linnemann¹,

Baan

Davis

2014

Advances in Nutrition

112

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Because obesity rates have increased dramatically over the past 3 decades, type 2 diabetes has become increasingly prevalent as well. Type 2 diabetes is associated with decreased pancreatic β-cell mass and function, resulting in inadequate insulin production. Conversely, in nondiabetic obesity, an expansion in β-cell mass occurs to provide sufficient insulin and to prevent hyperglycemia. This expansion is at least in part due to β-cell proliferation. This review focuses on the mechanisms regulating obesity-induced β-cell proliferation in humans and mice. Many factors have potential roles in the regulation of obesity-driven β-cell proliferation, including nutrients, insulin, incretins, hepatocyte growth factor, and recently identified liver-derived secreted factors. Much is still unknown about the regulation of β-cell replication, especially in humans. The extracellular signals that activate proliferative pathways in obesity, the relative importance of each of these pathways, and the extent of cross-talk between these pathways are important areas of future study.

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“…In recent years, animal models of insulin resistance have indicated the existence of circulating factors promoting pancreatic beta-cell proliferation, but the clinical implications of these factors are poorly understood due to a lack of specificity and uncertainty concerning their effects [5,6]. Betatrophin, a circulating protein, also referred to as lipasin [7], atypical angiopoietin-like 8 (ANGPTL8) [8], and refeeding-induced fat and liver protein (RIFL) [9], is a nutritionally regulated factor up-regulated by feeding and suppressed by fasting that plays a key role in fatty acid metabolism and lipid homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of circulating betatrophin levels in gestational diabetes mellitus

Erol¹,

Elli̇dağ

Ayik³

et al. 2015

Gynecological Endocrinology

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Experimental data indicate that betatrophin plays a significant role in the regulation of lipid metabolism and glucose homeostasis. In recent years, considerable attention has focused on the relationship between betatrophin and diabetes mellitus in humans. This case-control study included 45 women diagnosed with gestational diabetes mellitus (GDM) and 45 pregnant healthy controls. The groups were matched for maternal and gestational age and body mass index. Serum betatrophin levels were significantly higher in women with GDM (median = 635.8 ng/L; range: 290-1841.6 ng/L) compared to control subjects (median = 320.1 ng/L; range: 94.6-936.8 ng/L; p = 0.001). No significant correlations were observed between serum betatrophin levels and clinical or biochemical parameters in the control group. However, in the GDM group, serum betatrophin levels were positively correlated with weight gain during pregnancy (r = 0.304, p = 0.042), systolic blood pressure (r = 0.394, p = 0.007), fasting insulin level (r = 0.348, p = 0.019), and homeostatic model assessment insulin resistance (HOMA-IR; r = 0.311, p = 0.038). Multivariate stepwise linear regression analysis revealed that fasting insulin levels (β = 0.342, p = 0.022) and HOMA-IR (β = 0.312, p = 0.037) were independently associated with serum betatrophin levels.

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Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States

Cited by 16 publications

References 0 publications

Stress-activatedmiR-21/miR-21*in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption

Stress-activatedmiR-21/miR-21*in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption

Pancreatic β-Cell Proliferation in Obesity

Evaluation of circulating betatrophin levels in gestational diabetes mellitus

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