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| 1 | Betatrophin:A liver-derived hormone for the pancreatic β-cell proliferation显示文摘The pancreaticβ-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus(T2DM).The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections,neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas.A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreaticβ-cells that might obviate a need for exogenous insulin injections.A new study towards attaining this aim was reported by Yi et al,who have characterized a liver-derived protein,named betatrophin,capable of inducing pancreaticβ-cell proliferation in mice.Using a variety of in vitro and in vivo methods,Yi et al,have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice.Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreaticβ-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance.The authors discovered that betatrophin was also present in the human plasma.Surprisingly,betatrophin has been previously described by three other names,i.e.,re-feeding-induced fat and liver protein,lipasin and atypical angiopoeitin-like 8,by three independent laboratories,as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism.Yi et al demonstration of betatrophin,as a circulating hormone that regulatesβ-cell proliferation,if successfully translated in the clinic,holds the potential to change the course of current therapies for diabetes. | Rajendra Raghow | 2013 | World Journal of Diabetes2013，4，6： | 6 |
| 2 | Statins redux:A re-assessment of how statins lower plasma cholesterol显示文摘Obesity associated dyslipidemia and its negative effects on the heart and blood vessels have emerged as a major healthcare challenge around the globe. The use of statins, potent inhibitors of hydroxyl-methyl glutaryl(HMG) Co-A reductase, a rate-limiting enzyme in cholesterol biosynthesis, has significantly reduced the rates of cardiovascular and general mortality in patients with coronary artery disease. How statins lower plasma cholesterol levels presents a mechanistic conundrum since persistent exposure to these drugs in vitro or in vivo is known to induce overexpression of the HMG Co-A reductase gene and protein. In an attempt to solve this mechanistic puzzle, Schonewille et al, studied detailed metabolic parameters of cholesterol synthesis, interorgan flux and excretion in mice treated with 3 common statins, rosuvastatin, atorvastatin or lovastatin, each with its unique pharmacokinetics. From the measurements of the rates of heavy water(D_2O) and [^(13)C]-acetate incorporation into lipids, the authors calculated the rates of whole body and organ-specific cholesterol synthesis in control and statin-treated mice. These analyses revealed dramatic enhancement in the rates of hepatic cholesterol biosynthesis in statin-treated mice that concomitantly elicited lower levels of cholesterol in their plasma. The authors have provided strong evidence to indicate that statin treatment in mice led to induction of compensatory metabolic pathways that apparently mitigated an excessive accumulation of cholesterol in the body. It was noted however that changes in cholesterol metabolism induced by 3 statins were not identical. While sustained delivery of all 3 statins led to enhanced rates of biliary excretion of cholesterol and its fecal elimination, only atorvastatin treated mice elicited enhanced trans-intestinal cholesterol excretion. Thus, blockade of HMGCR by statins in mice was associated with profound metabolic adaptations that reset their cholesterol homeostasis. The findings of Schonewille et al, deserve to be corroborated and extended in patients in order to more effectively utilize these important cholesterol-lowering drugs in the clinic. | Rajendra Raghow | 2017 | World Journal of Diabetes2017，8，6： | 3 |
| 3 | Bariatric surgery-mediated weight loss and its metabolic consequences for type-2 diabetes显示文摘The worldwide epidemic of obesity and its medical complications are being dealt with a combination of life style changes(e.g.,healthier diet and exercise),medications and a variety of surgical interventions.The Roux-en Y gastric bypass(RYGB) and laparoscopic adjustable gastric banding(LAGB) are two of the most common weight loss surgeries for morbid obesityassociated metabolic syndrome and insulin resistance.A vast majority of patients that undergo RYGB and LAGB are known to experience marked weight loss and attenuation of diabetes.A number of recent studies have indicated that the rates of remission in glycemic control and insulin sensitivity are significantly greater in patients that have undergone RYGB.A plausible hypothesis to explain this observation is that the gastric bypass surgery as opposed to the gastric banding procedure impinges on glucose homeostasis by a weight loss-independent mechanism.In a recent paper,Bradley et al have experimentally explored this hypothesis.The authors compared several clinical and laboratory parameters of insulin sensitivity and β-cell function in cohorts of RYGB and LAGB patients before and after they lost approximately 20% of their body mass.Afterweight loss,both groups of patients underwent similar changes in their intra-abdominal and total adipose tissue volume,hepatic triglyceride and circulating leptin levels.The RYGB patients who lost 20% body mass,manifested higher postprandial output of glucose,insulin and glucagon-like peptide-1;these laboratory parameters remained unchanged in LABG patients.Irrespective of the observed differences in transient responses of RYGB and LAGB patients to mixed meal,the overall glycemic control as judged by glucose tolerance,multi-organ insulin sensitivity and β-cell function were nearly identical in the two groups.Both RYGB and LAGB patient cohorts also experienced similar changes in the expression of a number of pro-and anti-inflammatory markers.Based on these analyses,Bradley et al concluded that similar restoration of insulin sensitivity and b-cell function in non-diabetic obese patients that have undergone RYGB and LAGB were directly due to marked weight loss.These data have important implications for the risk/benefit analysis of weight loss therapy by bariatric procedures. | Rajendra Raghow | 2013 | World Journal of Diabetes2013，4，3： | 2 |
| 4 | Metabolic balancing acts of vitamin A in type-2 diabetes and obesity显示文摘Using mice that lack retinaldehyde dehydrogenase 1 gene(Raldh1-/-mice),Kierfer et al demonstrated that retinoids(metabolites of Vitamin A) play an important role in the regulation of cellular metabolisms and energetics.The Aldh1a1-/-mice were leaner and less prone to accumulate subcutaneous and visceral fat,and to acquire insulin resistance on high fat diet.Their lower fasting glucose levels concomitant with reduced hepatic expression of glucose 6-phosphatase and phosphoenol pyruvate carboxy kinase genes indicated that Aldh1a1-/-mice were defective in gluconeogenesis.These mice also had lower plasma levels of triglycerides,very low-density lipoprotein and lowdensity lipoprotein-triacylglycerol,while their skeletal muscles elicited higher expression of carnitine palmatoyl transferase,medium chain acyl-A dehydrogenase,peroxisome proliferation activated receptor(PPARα and PPARδ.Thus,the improved lipid and lipoprotein profiles of Raldh1a1-/-mice resulted from a combination of reduced lipogenesis and enhanced fatty acid oxidation by retinoids.The mechanistic details of how retinoids integrate fasting glucose,hepatic gluconeogenesis and adaptive thermogenesis independent of body mass deserve further study. | Rajendra Raghow | 2012 | World Journal of Diabetes2012，3，10： | 2 |
| 5 | SREBPs : the crossroads of physi- ological and pathological lipid homeostasis 显示文摘 | Raghow R Yellaturu C Deng X | 2008 | Trends Endocrinol Metab2008，19，2： | 1 |
| 6 | Extracellular matrix in normaland fibrotic human lungs 显示文摘 | Raghow R Streker LJ Hudson LD | 1985 | AM Bey Respir Dis1985，131，： | 1 |
| 7 | SREBPs:the crossroads of physiological and pathological lipid homeostasis 显示文摘 | Raghow R Yellaturu C Deng X | 2008 | Trends Endocrinol Metab2008，19，2： | 1 |
| 8 | SREBPs: the crossroads of physiological and pathological lipid homeostasis 显示文摘 | Raghow R Yellatnru C DENG X | 2008 | Trends in Endocrinology a:dMetabolism2008，19，2： | 1 |
| 9 | Murine Homeobox - Containing Gene, Msx - 1: Analysis of Genomic Organization, Promoter Structure, and Potential Autoregulatory cis -Acting Elements显示文摘 | Masahiko Kuzuoka Takayuki Takahashi Raghow R | 1994 | Genomics1994，21，1： | 1 |
| 10 | The tissue-specific,compensatory expression of cyclooxygenase 1 and -2 in transgenic mice 显示文摘 | Zhang J Goorha S Raghow R | 2002 | Prostaglandins Other Lipid Mediat2002，67，2： | 1 |
| 11 | The chimpanzee as a model of human benign prostatic hyperplasia 显示文摘 | Steiner MS Couch RC Raghow S | 1999 | J Urol1999，162，4： | 1 |
| 12 | The role of extracellular matrix in postin flammatory wound healing and fibrosis显示文摘 | Raghow R | 1994 | FASEB J1994，8，： | 1 |
| 13 | A pentapeptide from type Ⅰ procollagen promotes extracellular matrix production显示文摘 | Katayama K Armendariz-Borunda J Raghow R | | 0，，14： | 1 |
| 14 | Coordinate regulation of trans-forming growth factor beta gene expression and cell prolifera-tion in hamster lungs undergoing bleomycin-induced pulmo-nary fibrosis显示文摘 | Raghow R Irish P Kang AH | 1989 | J Clin Invest1989，84，6： | 1 |
| 15 | Transcriptional regulation of cyclooxygenase-2 in the human microvascular endothelial cell line, HMEC-1: Control by the combinatorial actions of AP2, NF-IL-6 and CRE elements显示文摘 | Kirtikara K Raghow R Laulederkind SJF | 2000 | Mol Cell Biochem2000，203，： | 1 |
| 16 | SREBPs : the cross- roads of physiological and pathological lipid homeostasis 显示文摘 | Raghow R Yellaturu C Deng X | 2008 | Trends Endocrinol Metab2008，19，2： | 1 |
| 17 | Compensatory prostaglandin E2 biosynthesis in cyclooxygenase 1 or 2 null cells显示文摘 | Kirtikara K Morham SG Raghow R | | 0，，： | 1 |
| 18 | Extrace cellular matrix in normal and fibrotic human lungs显示文摘 | Raghow R Streker LJ Hudson LD | 1985 | AmRevrespirDis1985，131，2： | 1 |
| 19 | Compensatory prostaglandin E2 biosynthesis in COX-1 or -2 null cells显示文摘 | MORHAM S G RAGHOW R | 1998 | J Exp Medicine1998，187，4： | 1 |
| 20 | SREBPs:the crossroads of physiological and pathological lipid homeostasis 显示文摘 | Raghow R Yellatum C Deng X | 2008 | Trends Endo- erinol Metab2008，19，2： | 1 |
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