JCMD Vol I Issue 1

Thiazolidinedione-induced Skeletal Fragility

Andrew Grey

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Angiopoietin-like Protein 4—A Novel Communicator Between Muscle and Fat

Staiger Harald, Thamer Claus, Häring Hans-Ulrich

Abstract

Angiopoietin-like Protein 4—A Novel Communicator Between Muscle and Fat

Staiger H, Thamer C, Haring HU. Angiopoietin-like Protein 4 – A Novel Communicator Between Muscle and Fat. Journal of Clinical Metabolism and Diabetes. May 2010; 1(1): 9-18

REVIEW ARTICLE

Angiopoietin-like Protein 4—A Novel Communicator Between Muscle and Fat

Harald Staiger^1,2,Claus Thamer^1,2 and Hans-Ulrich Häring^1,2

Affiliations: ¹Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany and ²German Centre for Diabetes Research (DZD), Eberhard Karls University Tübingen, , Tübingen, Germany

ABSTRACT

Insulin-sensitive tissues, such as muscle, liver, fat, and brain, fine-tune their energy metabolism via a complex network of circulating metabolites and hormones. Chronic disturbances of this network are thought to contribute to metabolic disorders like obesity and insulin resistance. During the last few years, several metabolically relevant hormones produced by skeletal muscle, nowadays collectively termed myokines, were identified. The recently recognized myokine angiopoietin-like protein 4 (ANGPTL4) is produced and secreted upon peroxisome proliferator-activated receptor δ (PPARδ) activation by long-chain nonesterified fatty acids and stimulates adipose tissue lipolysis. In this way, ANGPTL4 supplies the fasting as well as the exercised muscle—both characterized by increased PPARδ activity-with fatty acids and supports PPARδ-triggered fatty acid oxidation. Thus, elevation of muscle-derived ANGPTL4 may be a promising approach to reduce fat mass and to deplete intramyocellular lipids. However, ANGPTL4 is a two-edged sword: it also potently inhibits lipoprotein lipase; this function on the one hand may further contribute to fat loss, but on the other hand results in hypertriglyceridemia and hepatic steatosis, well-known risk factors for coronary heart disease and type 2 diabetes. Since ANGPTL4 may indeed represent an interesting novel target for the therapy of obesity and obesity-associated insulin resistance, much more has to be learned about this protein's biology to find ways to bypass its undesirable effects. The present review summarizes the current knowledge about ANGPTL4's structural features and its regulated expression/secretion, as well as its biological functions, and describes its novel role as a myokine.

Keywords: ANGPTL4, PPARδ, fatty acids, lipolysis, LPL

Abbreviations: ANGPT, angiopoietin; ANGPTL, angiopoietin-like protein; IL, interleukin; NEFA, nonesterified fatty acids; PPAR, peroxisome proliferator-activated receptor; SNP, single nucleotide polymorphism; VLDL, very-low-density lipoproteins.

Correspondence: Prof. Dr. rer. nat. Harald Staiger, Internal Medicine IV, University Hospital Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. Tel: +49-7071-29-85774; Fax: +49-7071-29-5277; e-mail: harald.staiger@med.uni-tuebingen.de

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ß-blocker Treatment is Associated with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes

Wijkman M, Länne T, Engvall J, Lindström T, Östgren CJ, Nystrom FH

Abstract

ß-blocker Treatment is Associated with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes

Wijkman M, Lanne T, Engvall J, Lindstrom T, Ostgren CJ, Nystrom FH. B-Blocker Treatment is Associted with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes. Journal of Clinical Metabolism & Diabetes, June 2010; 1(1): 9-15

ORIGINAL ARTICLE

ß-blocker Treatment is Associated with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes

M Wijkman^1,2, T Länne^1, J Engvall^1, T Lindström^1,2, CJ Östgren^1,2 and FH Nystrom^1,2

Affiliations: ¹Department of Medical and Health Sciences, Linköping University, Linköping, Sweden and ²Diabetes Research Centre, Linköping University, Linköping, Sweden

ABSTRACT

Aims: To explore the associations between ß-blocker treatment and clinic, ambulatory, and central pulse pressure (PP) and central augmentation index (AIx), and left ventricular mass index (LVMI), respectively, in patients with type 2 diabetes.
Methods: In 124 middle-aged patients with type 2 diabetes who were treated in primary care and used at least one antihypertensive drug, we measured clinic PP (mean value of three nurse-recorded measurements in the sitting position) and ambulatory PP (24-hour ambulatory measurements with the Spacelab 90217 measurement device). Central PP was measured non-invasively, using applanation tonometry (SphygmoCor), which also yielded values of AIx. LVMI was determined echocardiographically in all patients.
Results: Patients whose antihypertensive drug regimen included a ß-blocker (n=67) had significantly higher central PP compared with patients whose antihypertensive drug regimen did not include a ß-blocker (ß-blocker: 49.6±12.2 mmHg, no ß-blocker: 45.1±10.2 mmHg; p=0.03) despite having similar clinic PP (ß-blocker: 60.4±16.3 mmHg, no ß-blocker: 58.9±13.1 mmHg; p=0.59) and similar ambulatory PP (ß-blocker: 55.2±9.1 mmHg, no ß-blocker: 54.8±10.6 mmHg; p=0.40). Patients treated with ß-blockers also had significantly higher AIx (ß-blocker: 30.7±8.4%, no ß-blocker: 25.8±8.8%; p<0.01) and higher LVMI (ß-blocker: 129.5±29.7 g/m2, no ß-blocker: 117.4±27.4 g/m2; p=0.02) compared with patients who were not treated with ß-blockers.
Conclusions: In our cohort, ß-blocker use was associated with high central but not brachial PP and with high central AIx and high LVMI. Non-invasive measurement of central hemodynamic parameters may improve the evaluation of antihypertensive treatment efficacy in patients with type 2 diabetes.

Keywords: ß-blockers, cardiac mass, diabetes, hypertension, pulse pressure

Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; AIx, augmentation index; BP, blood pressure; CARDIPP, cardiovascular risk factors in patients with diabetes—a prospective study in primary care; LVH, left ventricular hypertrophy; LVMI, left ventricular mass index; PP, pulse pressure; PWV, pulse wave velocity.

Correspondence: Magnus Wijkman, Department of Medical and Health Sciences, Linköping University, S-581 83 Linköping, Sweden. Tel: +46 70 3232211; Fax: +46 11 223571; e-mail: magnus.wijkman@liu.se

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Hepatic PTP1B Deficiency: The Promise of a Treatment for Metabolic Syndrome?

Kendra K Bence

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Metabolic Actions of Xenin

Tooru M Mizuno

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The Association Between Soluble P-selectin and Insulin Sensitivity in Healthy Humans

Kevin J Woollard, Maximilian PJ de Courten, Karly C Sourris et al

Abstract

The Association Between Soluble P-selectin and Insulin Sensitivity in Healthy Humans

Wollard KJ, de Courten MPJ, Sourris KC, Drew BG, Henstridge DC, Kingwell B, Cooper MM, Howlett KF, Forbes JM, de Couten B. The Association Between Soluble P-selectin and Insulin Sensitivity in Healthy Humans. Journal of Clinical Metabolism & Diabetes, May 2010; 1(1): 19-26

Kevin J Woollard^1, Maximilian PJ de Courten^2, Karly C Sourris^1, Brian G Drew^1, Darren C Henstridge^1, Bronwyn Kingwell^1, M Mark Cooper^1, Kirsten F Howlett^3, Josephine M Forbes¹ and Barbora de Courten¹

Affiliations: ¹Baker IDI Heart and Diabetes Institute, Metabolic and Vascular Physiology Laboratory, Melbourne, Victoria, Australia; ²School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia and ³Deakin University, Centre for Physical Activity and Nutrition Research, Melbourne, Victoria, Australia

ABSTRACT

OBJECTIVE
Adhesion molecules play a pivotal role in atherosclerosis and some have been shown to be associated with insulin resistance and type 2 diabetes. Soluble P-selectin (sP-selectin) plays a key role in leukocyte rolling and adhesion and contributes to the development of cardiovascular disease and unstable plaque. Despite their important role in inflammation, there is a paucity of data on the part of P-selectin in the development of insulin resistance. Therefore, we investigated whether plasma adhesion molecules and in particular sP-selectin are related to insulin sensitivity.
RESEARCH DESIGN AND METHODS
Fasting plasma sP-selectin (ELISA), ICAM-1, VCAM-1, adiponectin (Bioplex), adiposity (DEXA), waist-to-hip ratio (WHR), insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), fitness (VO2max), and habitual physical activity (iPAQ questionnaire) were assessed in 22 non-diabetic volunteers (10 females, 12 males) aged 29±(11 years (mean±SD).
RESULTS
sP-selectin levels were associated with WHR before and after adjustment for age and sex (p=0.03), but not percent body fat (p>0.1). sP-selectin levels correlated with plasma adiponectin levels before and after adjustment for age, sex, body fat, and WHR (p=0.005). sP-selectin levels were also associated with insulin sensitivity (r=–0.60, p=0.03) independent of age, sex, percent body fat, and WHR (p=0.02, respectively), however, the association disappeared after additional adjustment for plasma adiponectin levels (p=0.3). There was no relationship between plasma levels of ICAM-1 or VCAM-1 and any of the anthropometric or metabolic variables (all p>0.1). There was no relationship between adhesion molecules and measures of physical activity (p>0.1).
CONCLUSIONS
In this cohort, plasma sP-selectin was negatively associated with insulin sensitivity independently of obesity and this relationship may be mediated by adiponectin.

Keywords: adhesion molecules, sP-selectin, ICAM-1, VCAM-1, inflammation, insulin resistance, obesity, adiponectin

Correspondence: Barbora de Courten, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne VIC 3004, Australia. Tel: +61 3 8532 1353; Fax: +61 3 8532 1111; e-mail: barbora.decourten@bakeridi.edu.au

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Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors

Kaj Stenlöf

Abstract

Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors

Stenlof K. Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors. Journal of Clincial Metabolism and Diabetes, May 2010; 1(1): 1-7

Kaj Stenlöf

Affiliation: Department for Clinical Research, The Sahlgrenska University Hospital, Gothenburg, Sweden

ABSTRACT

Obesity is a serious health concern in several parts of the world. During the last few years, the prevalence of abdominal obesity has attracted specific attention, as abdominal obesity and visceral obesity are associated with several important metabolic disturbances and explain most of the increased risk for cardiovascular disease (CVD) associated with obesity. Thus, in the clinical evaluation of obese patients with an increased risk for CVD, it is important to aim to reduce abdominal fat. Lifestyle interventions, including diet and physical activity, should be first-line treatments; however, pharmaceutical agents might also be considered. Not surprisingly, abdominal and visceral obesity are important targets for drug development. Orlistat is an existing pharmacological agent available for the long-term treatment of obesity. This drug inhibits gastric and pancreatic lipase degradation of triglycerides in the intestine, such that ingested triglycerides cannot be hydrolyzed or absorbed. Orlistat has been investigated in several large studies that demonstrated its efficacy and safety, and is currently available in more than 120 countries, with more than 40 million doses having been distributed worldwide (www.fda.gov/Drugs/, May 2010). The purpose of this report is to provide a short review of the available data regarding the effects of orlistat on abdominal obesity and associated metabolic disturbances.

Keywords: abdominal obesity, orlistat, hyperglycemia, dyslipidemia, hypertension, atherosclerosis, cardiovascular disease

Correspondence: Kaj Stenlöf, Department for Clinical Research, The Sahlgrenska University Hospital, Gröna stråket 12, SE-413 45 Gothenburg, Sweden. Tel: +46 31 342 10 00; Fax: +46 31 41 93 68; e-mail: kaj.stenlof@vgregion.se

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Bioprotein Glycosylation Process in Poorly Controlled Diabetes: New Approach and Implications

Viroj Wiwanitkit

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Lifestyle Modification as a Tool for Primary Prevention of Type 2 Diabetes

Ambady Ramachandran and Chamukuttan Snehalatha

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JCMD Volume I Issue 1

Thiazolidinedione-induced Skeletal Fragility

Thiazolidinedione-induced Skeletal Fragility

Angiopoietin-like Protein 4—A Novel Communicator Between Muscle and Fat

Angiopoietin-like Protein 4—A Novel Communicator Between Muscle and Fat

ß-blocker Treatment is Associated with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes

ß-blocker Treatment is Associated with High Augmentation Index and with High Aortic, but not Brachial, Pulse Pressure in Type 2 Diabetes

Hepatic PTP1B Deficiency: The Promise of a Treatment for Metabolic Syndrome?

Hepatic PTP1B Deficiency: The Promise of a Treatment for Metabolic Syndrome?

Metabolic Actions of Xenin

Metabolic Actions of Xenin

The Association Between Soluble P-selectin and Insulin Sensitivity in Healthy Humans

The Association Between Soluble P-selectin and Insulin Sensitivity in Healthy Humans

Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors

Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors

Bioprotein Glycosylation Process in Poorly Controlled Diabetes: New Approach and Implications

Bioprotein Glycosylation Process in Poorly Controlled Diabetes: New Approach and Implications

Lifestyle Modification as a Tool for Primary Prevention of Type 2 Diabetes

Lifestyle Modification as a Tool for Primary Prevention of Type 2 Diabetes

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