Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes
The hormone betatrophin was recently described as a potent stimulator of beta cell proliferation in mice. Insulin resistance, but not insulin deficiency, caused upregulation of betatrophin expression. If these findings were found to be fully applicable in humans, this would open up the possibility of future betatrophin treatment in type 1 diabetes. The present study measured for the first time betatrophin concentrations in humans and tested the hypothesis that there would be no difference in circulating betatrophin concentrations between patients with type 1 diabetes and healthy individuals.
Betatrophin concentrations in plasma of 33 patients with type 1 diabetes and 24 age-matched healthy controls were measured by ELISA. The study participants were characterised for blood lipids, BMI, plasma glucose and HbA1c, and, for the diabetic patients, their insulin requirements and any residual C-peptide concentrations.
Plasma betatrophin concentrations were normally ∼300 pg/ml, but were approximately doubled in patients with type 1 diabetes. In the patients, there were no correlations between betatrophin and age, blood lipids, BMI, glucose control or insulin requirement, whereas in controls betatrophin levels increased with age. BMI, blood pressure and triacylglycerol, LDL-cholesterol and HDL-cholesterol levels were similar in patients and healthy controls.
Circulating concentrations of betatrophin are increased in type 1 diabetes in contrast with what was recently described in an insulin-deficient mouse model. However, increased betatrophin concentrations do not protect against loss of C-peptide. Betatrophin treatment in type 1 diabetes would therefore probably not be successful without the use of supraphysiological doses or a combination with immune regulatory treatment.
- Wang L, Lovejoy NF, Faustman DL (2012) Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care 35:465–470 CrossRef
- Keenan HA, Sun JK, Levine J et al (2010) Residual insulin production and pancreatic ss-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 59:2846–2853 CrossRef
- Yi P, Park JS, Melton DA (2013) Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell 153:747–758 CrossRef
- Cleland SJ, Fisher BM, Colhoun HM, Sattar N, Petrie JR (2013) Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? Diabetologia 56:1462–1470 CrossRef
- Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ (2000) Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 49:626–632 CrossRef
- Zhang R (2012) Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun 424:786–792 CrossRef
- Quagliarini F, Wang Y, Kozlitina J et al (2012) Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A 109:19751–19756 CrossRef
- Dong XY, Pang XW, Yu ST et al (2004) Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer 112:239–248 CrossRef
- Butler AE, Galasso R, Meier JJ, Basu R, Rizza RA, Butler PC (2007) Modestly increased beta cell apoptosis but no increased beta cell replication in recent-onset type 1 diabetic patients who died of diabetic ketoacidosis. Diabetologia 50:2323–2331 CrossRef
- Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG (2010) Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes. Diabetologia 53:2020–2028 CrossRef
- Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes
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Volume 57, Issue 1 , pp 50-53
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