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1.  IMPACT OF OBESITY SEVERITY AND DURATION ON PANCREATIC β-AND α-CELLS DYNAMICS IN NORMOGLYCEMIC NON-HUMAN PRIMATES 
Objective
Obesity is associated to high insulin and glucagon plasma levels. Enhanced β–cell function and β–cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons.
Methods
Pancreatic β- and α-cell volumes were measured in 51 normoglycemic baboons divided into 6 groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters.
Results
Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater, increase in RIαV. Baboons' body weights correlated with serum levels of Interleukin-6 and Tumour Necrosis Factor-α soluble Receptors (IL-6sR and sTNF-R1), demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β- and α-cell viability and replication.
Conclusion
In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV) while have minimal effects on the β-cells. This study suggests that an increase in the α-cell mass may precede the loss of β-cells and the transition to overt hyperglycemia and diabetes.
doi:10.1038/ijo.2012.205
PMCID: PMC3906680  PMID: 23229736
Obesity duration; obesity severity; α-cell volume; β-cells volume; pancreatic islet remodelling; insulin resistance
2.  Energy Expenditure Evaluation in Humans and Non-Human Primates by SenseWear Armband. Validation of Energy Expenditure Evaluation by SenseWear Armband by Direct Comparison with Indirect Calorimetry 
PLoS ONE  2013;8(9):e73651.
Introduction
The purpose of this study was to compare and validate the use of SenseWear Armband (SWA) placed on the arm (SWA ARM) and on the back (SWA BACK) in healthy humans during resting and a cycle-ergometer exercise and to evaluate the SWA to estimate Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) in healthy baboons.
Methods
We studied 26 (15F/11M) human subjects wearing SWA in two different anatomical sites (arm and back) during resting and a cycle-ergometer test and directly compared these results with indirect calorimetry evaluation (IC), performed at the same time. We then inserted the SWA in a metabolic jacket for baboons and evaluated the TEE and REE in free living condition for 6 days in 21 (8F/13M) non-human primates.
Results
In humans we found a good correlation between SWA place on the ARM and on the BACK with IC during the resting experiment (1.1±0.3 SWAs, 1±0.2 IC kcal/min) and a slight underestimation in the SWAs data compared with IC during the cycle-ergometer exercise (5±1.9 SWA ARM, 4.5±1.5 SWA BACK and 5.4±2.1 IC kcal/min). In the non-human primate (baboons) experiment SWA estimated a TEE of 0.54±0.009 kcal/min during free living and a REE of 0.82±0.06 kcal/min.
Conclusion
SWA, an extremely simple and inexpensive apparatus, provides quite accurate measurements of energy expenditure in humans and in baboons. Energy expenditure data obtained with SWA are highly correlated with the data obtained with “gold standard”, IC, in humans.
doi:10.1371/journal.pone.0073651
PMCID: PMC3777938  PMID: 24069218
3.  The Ontogeny of the Endocrine Pancreas in the Fetal/Newborn Baboon 
The Journal of endocrinology  2012;214(3):289-299.
Background
Erratic regulation of glucose metabolism including hyperglycemia is a common condition of premature infants and is associated with increased morbidity and mortality.
Objective
To examine histological and ultra-structural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons.
Methods
Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140dGA, or 175dGA. Eight animals were delivered at term (185dGA); half were fed for 5d. Seventy-three non-diabetic adult baboons were used for comparison. Pancreatic tissue was studied utilizing light microscopy, confocal imaging and electron microscopy.
Results
The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of α-β-δ-cell type were similar within each fetal and newborn GA (NS), but were higher than the adults (P<0.05) regardless of GA. The ratio of β-cells within the islet (whole and core) increased with gestation (P<0.01). Neonatal baboons who survived for 5 days (feeding), had a 2.5-fold increase in pancreas weight compared to their counterparts euthanized at birth (P=0.01). Endocrine cells were found amongst exocrine ductal and acinar cells in 125,140 and 175dGA fetuses. Subpopulation of cells that co-expressed trypsin and glucagon/insulin show the presence of cells with mixed endo-exocrine lineage in fetuses.
Conclusions
The fetal endocrine pancreas has no prevalence of a of α-β-δ-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long term implications.
doi:10.1530/JOE-12-0070
PMCID: PMC3686495  PMID: 22723715
Insulin; glucagon; fetus; islet cells; primates
4.  Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates 
PLoS ONE  2011;6(11):e27617.
Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.
Aims
To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity.
Methods
Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance.
Results
Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons.
Conclusion
Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.
doi:10.1371/journal.pone.0027617
PMCID: PMC3220682  PMID: 22125617
5.  Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons 
Background
Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available.
Methods
We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp.
Results
In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001).
Conclusion
In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus.
doi:10.1186/1475-2840-8-22
PMCID: PMC2674590  PMID: 19389241

Results 1-5 (5)