PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-11 (11)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
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.  The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus 
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy.
doi:10.5114/aoms.2013.34991
PMCID: PMC3832818  PMID: 24273582
meglitinide; repaglinide; nateglinide; glycemic control; post-prandial glucose excursion; hypoglycemia
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.  Spontaneous Pathology of the Baboon Endocrine System 
Journal of medical primatology  2009;38(6):383-389.
Background
Study of endocrine pathology in animal models is critical to understanding endocrine pathology in humans.
Methods
We evaluated 434 endocrine-related diagnoses from 4,619 baboon necropsies, established the incidence of spontaneous endocrine pathology, and analyzed the clinical and biochemical data associated with the individual cases.
Results
The most common diagnoses in descending order, were pancreatic islet cell amyloidosis (n=259), ovarian cysts (n=50), pituitary adenoma (n=37), pancreatic islet cell adenoma (n=20), granulosa cell tumor (n=15), thyroid adenoma (n=11), adrenal hyperplasia (n=10), thyroid carcinoma (n=8), and pheochromocytoma (n=6). The incidence of pancreatic islet cell amyloidosis progressively increased with age. Pheochromocytomas were associated with renal and heart failure. The incidence of pancreatic islet cell amyloidosis and adrenal pathology was similar to humans; the incidence of pituitary adenoma and thyroid pathology was lower than in humans.
Conclusions
Endocrine disease in baboons is common and shares clinical and biochemical characteristics with endocrine disease in humans.
doi:10.1111/j.1600-0684.2009.00384.x
PMCID: PMC2783813  PMID: 19793179
Papio; nonhuman primate; thyroid; pancreas; endocrine; disease; cancer
6.  Spontaneous Heart Disease in the Adult Chimpanzee (Pan troglodytes) 
Journal of medical primatology  2008;38(1):51-58.
Background
A high incidence of heart disease, especially idiopathic cardiomyopathy, is seen in chimpanzees (Pan troglodytes).
Methods
We reviewed clinical records and necropsy reports of 87 adult chimpanzees for possible causes of heart disease/idiopathic cardiomyopathy. We examined age, sex, cause of death, weight, diet, environment, infectious diseases, experimental uses, and clinical pathology.
Results
The overall prevalence of heart disease in chimpanzees was 67.81%; the prevalence of idiopathic cardiomyopathy was 51.72%. The prevalence of idiopathic cardiomyopathy was significantly higher in males (60.32%) than females (29.17%, p=0.009). The prevalence of other heart disease was higher in females (25%) than males (12.70%, p=0.165). Heart failure occurred in 47.13% of chimpanzees. Heart disease was the primary cause of death in 34.49% of chimpanzees; 29.88% died of unknown causes.
Conclusions
We found no evidence that diet, environment, viral agents, experimental use or disease exposure contributed to the deaths resulting from idiopathic cardiomyopathy in chimpanzees.
doi:10.1111/j.1600-0684.2008.00307.x
PMCID: PMC2933140  PMID: 18671767
ape; cardiomyopathy; atherosclerosis; arteriosclerosis; nonhuman primate
7.  Spontaneous Squamous Cell Carcinomas in 13 Baboons, a First Report in a Spider Monkey, and a Review of the Nonhuman Primate Literature 
Journal of medical primatology  2009;38(3):175-186.
Background
Squamous cell carcinoma (SCC) is a neoplastic proliferation of epithelial cells undergoing squamous differentiation and represents a diagnostic challenge in nonhuman primates (NHP), especially in baboons with perineal SCC.
Methods
Fourteen SCC (13 baboons, 1 spider monkey) were identified over a 20-year period. A literature search identified 86 additional published cases of spontaneous NHP SCC.
Results
SCC was most commonly reported in macaques, baboons, marmosets, and squirrel monkeys. Metastasis occurred in 23%, of NHP. The most frequently reported primary locations were the oral cavity, integument, esophagus, and cervix-uterus. Perineal SCC occurred mainly in baboons. All reported SCC in marmosets occurred in the head. Nasal cavity SCC was only reported in male marmosets. All reported pulmonary SCC occurred in males, mostly in tree shrews.
Conclusions
SCC is a common neoplasm in NHP and exhibits species differences. NHPs may provide a useful SCC animal model.
doi:10.1111/j.1600-0684.2009.00338.x
PMCID: PMC2919327  PMID: 19220686
Cancer; neoplasm; Papio; skin; oral cavity; esophagus
8.  Nonspecific Lymphocytic Myocarditis in Baboons Is Associated with Trypanosoma cruzi Infection 
Non-specific lymphocytic myocarditis (NLM) is frequently observed in baboons within the endemic range of Trypanosoma cruzi. We sought to determine whether T. cruzi infection is a cause of baboon NLM. We evaluated serial histologic sections of cardiac muscle, blood cultures, immunohistochemistry, serology, polymerase chain reaction, and clinical pathology from 31 baboons with NLM to determine whether T. cruzi infection is associated with NLM. Eleven baboons with no evidence of T. cruzi infection by serology and no NLM were used as controls. Seropositivity for T. cruzi was 45% in baboons with NLM compared with a 2–3% colony prevalence. NLM lesion severity was significantly higher in seropositive than seronegative baboons with NLM. NLM was significantly more common in older baboons. No statistical association between NLM and sex, weight, or clinical pathology was found. These results suggest an association between NLM and T. cruzi infection in the baboon.
PMCID: PMC2740900  PMID: 19635876
9.  Neoplasia in the Chimpanzee (Pan spp.) 
Journal of medical primatology  2009;38(2):137-144.
Background
Chimpanzees have over 98% genomic sequence homology with humans and may have a similar host response to malignancy. There is minimal information concerning cancer in the chimpanzee and such information would be valuable to individuals caring for and using them for research.
Methods
Spontaneous neoplasia that was documented in two chimpanzee colonies and in the literature were evaluated statistically.
Results
In all, 105 spontaneous and 12 experimental neoplasms were diagnosed. Seventy-four spontaneous tumors occurred in females, 24 in males, and 7 in animals of undetermined sex. Of the spontaneous tumors 89 were benign, 14 were malignant, and 2 were undetermined.
Neoplasia was most common in the urogenital system in females.
Conclusions
Neoplasia is not uncommon in the chimpanzee, is generally benign, and occurs primarily in the urogenital system in females.
PMCID: PMC2893876  PMID: 19367738
Ape; nonhuman primate; cancer; tumor; disease; leiomyoma
10.  Stillbirths in Macaca fascicularis 
Journal of medical primatology  2008;37(4):169-172.
Background
Stillbirths in nonhuman primates are a major problem and represent failure of the maternal-fetal-placental unit to maintain normal relationships due to various endogenous, undetermined, or environmental factors.
Methods
Records of 236 stillborns and their dams in a Macaca fascicularis colony during a 7-year period were reviewed retrospectively.
Results
The 7-year stillbirth incidence was 11.99% (236 stillbirths, 1,968 live births). Most (61.02%, n=144) were of undetermined etiology. Fetal causes included trauma (22.46%, n= 53), fetal pneumonia (0.85%, n=2) and congenital anomalies (0.42%, n=1). Maternal causes included dystocia (9.75%, n=23), placental abruption (0.85%, n=2), and uterine rupture (0.42 %, n=1). Forty-nine placentas were available for histologic evaluation; there was placentitis in five and necrosis in five. Most stillbirths occurred close to term. First stillbirths usually occurred in 8- to 12-year-old animals during the first six pregnancies.
Conclusions
Most stillbirths were of undetermined etiology. Fetal trauma was the most common cause.
doi:10.1111/j.1600-0684.2007.00275.x
PMCID: PMC2574872  PMID: 18194223
Stillborn; reproduction; cynomolgus; fetus; placenta; dystocia; nonhuman primate
11.  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 1-11 (11)