Polymorphism rs3123554 in the cannabinoid receptor gene type 2 ( CNR2 ) reveals effects on body weight and insulin resistance in obese subjects

BACKGROUND: Managing diabetes is difficult due to the number of side effects associated with drugsused for its treatment. There it is a need of an hour to look for indigenous plants which are safe and costeffective. Present study was planned to determine the effect of Aloe vera whole leaf extract and/orRosiglitazone on plasma glucose, insulin and insulin resistance in type 2 diabetic Sprague-Dawley rats.DESIGN: Randomized control trailPLACE AND DURATION OF STUDY: This study was conducted from April 2009 to Oct 2010 at theDepartment of Physiology Army Medical College, Rawalpindi in collaboration with National Institute ofHealth (NIH) Islamabad.MATERIAL AND METHOD: Type 2 DM was induced in 60 healthy Sprague-Dawley rats by feedinghigh fat diet for 2 weeks and injecting a low dose (35mg/kg) of streptozotocin intra peritoneally. Type 2diabetic rats were randomly divided into four groups, each group having 15 rats and were labeled as diabeticgroup, Aloe vera group, rosiglitazone group and combined group. The diabetic group was injected normalsaline, Aloe vera group was treated with Aloe vera whole leaf extract in dose of 300mg/kg body weight,rosiglitazone group was given 5mg/kg body weight of rosiglitazone I/P and combined group diabetic ratswere treated with 150mg/kg body weight of Aloevera extract and 2.5mg/kg body weight of rosiglitazone(halfof their effective dose) for 21 days.RESULTS: A significant reduction (p<0.001) in plasma glucose (73%), insulin (32%) and TG/HDL ratio(81%) was analyzed in combined groupascompared to diabetic control group. \CONCLUSION: The maximum impact in lowering plasma glucose, insulin and TG/HDL ratio wasrecorded in combined group, followed by rosiglitazone group and then Aloevera group.KEYWORDS:T2DM. Aloe vera, insulin resistance

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Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes

Acta Endocrinologica ◽

10.1530/eje-12-0374 ◽

2012 ◽

Vol 167 (4) ◽

pp. 569-578 ◽

Cited By ~ 34

Author(s):

Francisco J Ortega ◽

Mónica Sabater ◽

José M Moreno-Navarrete ◽

Neus Pueyo ◽

Patricia Botas ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Weight Loss ◽

Lipid Metabolism ◽

Inflammatory Markers ◽

Low Grade ◽

Model Assessment ◽

Glucose And Lipid Metabolism ◽

Obese Subjects

ObjectiveIncreased circulating calprotectin has been reported in obese subjects but not in association with measures of insulin resistance and type 2 diabetes (T2D). The main aim of this study was to determine whether calprotectins in plasma and urine are associated with insulin resistance.DesignWe performed both cross-sectional and longitudinal (diet-induced weight loss) studies.MethodsCirculating calprotectin concentrations (ELISA), other inflammatory markers, homeostasis model assessment of insulin resistance (HOMA-IR), and parameters of glucose and lipid metabolism were evaluated in 298 subjects (185 with normal (NGT) and 62 with impaired (IGT) glucose tolerance and 51 T2D subjects). Calprotectin was also evaluated in urine samples from 71 participants (50 NGT and 21 subjects with IGT). Insulin sensitivity (SI, Minimal Model) was determined in a subset of 156 subjects, and the effects of weight loss were investigated in an independent cohort of obese subjects (n=19).ResultsCirculating calprotectin was significantly increased in IGT–T2D (independently of BMI) and positively associated with HOMA-IR, obesity measures, inflammatory markers, and parameters of glucose and lipid metabolism. Similar findings were reported for calprotectin concentrations in urine. In the subset of subjects, the association of calprotectin withSIwas independent of BMI and age. In fact,SItogether with C-reactive protein contributed to 27.4% of calprotectin variance after controlling for age and blood neutrophils count. Otherwise, weight loss led to decreased circulating calprotectin in parallel to fasting glucose and HOMA-IR.ConclusionThese findings suggest that circulating and urinary concentrations of calprotectin are linked to chronic low-grade inflammation and insulin resistance beyond obesity.

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Autoimmunity, Insulin Resistance and Beta Cell Function in Subjects with Low Body Weight Type 2 Diabetes Mellitus

Metabolic Syndrome and Related Disorders ◽

10.1089/met.2006.0024 ◽

2007 ◽

Vol 5 (2) ◽

pp. 136-141 ◽

Cited By ~ 9

Author(s):

Sidhartha Das ◽

Sanjeev Kumar Bhoi ◽

A.K. Baliarsinha ◽

Mirza Asraf Ali Baig

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function

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Effects of Trp64Arg Mutation in the 3-Adrenergic Receptor Gene on Weight Loss, Body Fat Distribution, Glycemic Control, and Insulin Resistance in Obese Type 2 Diabetic Patients

Diabetes Care ◽

10.2337/diacare.20.12.1887 ◽

1997 ◽

Vol 20 (12) ◽

pp. 1887-1890 ◽

Cited By ~ 80

Author(s):

N. Sakane ◽

T. Yoshida ◽

T. Umekawa ◽

A. Kogure ◽

Y. Takakura ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Loss ◽

Adrenergic Receptor ◽

Receptor Gene ◽

Fat Distribution ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic ◽

Adrenergic Receptor Gene

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Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

International Journal of Molecular Sciences ◽

10.3390/ijms20092109 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2109 ◽

Cited By ~ 6

Author(s):

Arulkumar Nagappan ◽

Jooyeon Shin ◽

Myeong Ho Jung

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Insulin Sensitivity ◽

Hepatic Steatosis ◽

Cannabinoid Receptor ◽

Inflammatory Responses ◽

Hepatic Insulin Resistance ◽

Leptin Resistance ◽

Peripheral Tissues

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

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