Pleiotropic Effects of Genes for Insulin Resistance on Adiposity in Baboons

Cai, Guowen; Cole, Shelley A.; Tejero, Maria Elizabeth; Proffitt, J. Michael; Freeland‐Graves, Jeanne H.; Blangero, John; Comuzzie, Anthony G.

doi:10.1038/oby.2004.219

Cited by 33 publications

(26 citation statements)

References 36 publications

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“…As in humans, most NHPs with diabetes have T2DM (Wagner et al 1996b(Wagner et al , 2001. Similar to humans, T2DM is associated with increasing age and body weight in rhesus (Hamilton and Ciaccia 1978;Hotta et al 2001), in cynomolgus monkeys (Wagner et al 1996b), and in baboons (Banks et al 2003;Cai et al 2004;Stokes 1986). The disease initially is associated with normal glucose tolerance and insulin resistance with compensatory hyperinsulinemia, followed by continued deterioration of carbohydrate metabolism ( Figure 1) (Hansen and Bodkin 1986).…”

Section: Overview Of Diabetes In Old World Nhpsmentioning

confidence: 91%

Old World Nonhuman Primate Models of Type 2 Diabetes Mellitus

Wagner

Kavanagh²,

Ward³

et al. 2006

ILAR Journal

159

153

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Type 2 diabetes mellitus is a major health problem of increasing incidence. To better study the pathogenesis and potential therapeutic agents for this disease, appropriate animal models are needed. Old World nonhuman primates (NHPs) are a useful animal model of type 2 diabetes; like humans, the disease is most common in older, obese animals. Before developing overt diabetes, NHPs have a period of obesity-associated insulin resistance that is initially met with compensatory insulin secretion. When either a relative or absolute deficiency in pancreatic insulin production occurs, fasting glucose concentrations begin to increase and diabetic signs become apparent. Pathological changes in pancreatic islets are also similar to those seen in human diabetics. Initially there is hyperplasia of the islets with abundant insulin production typically followed by replacement of islets with islet-associated amyloid. Diabetic NHPs have detrimental changes in plasma lipid and lipoprotein concentrations, lipoprotein composition, and glycation, which may contribute to progression of atherosclerosis. As both the prediabetic condition (similar to metabolic syndrome in humans) and overt diabetes become better defined in monkeys, their use in pharmacological studies is increasing. Likely due to their genetic similarity to humans and the similar characteristics of the disease in NHPs, NHPs have been used to study recently developed agonists of the peroxisome proliferators-activated receptors. Importantly, agonists of the different receptor subclasses elicit similar responses in both humans and NHPs. Thus, Old World NHPs are a valuable animal model of type 2 diabetes to study disease progression, associated risk factors, and potential new treatments.

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Section: Overview Of Diabetes In Old World Nhpsmentioning

confidence: 91%

Old World Nonhuman Primate Models of Type 2 Diabetes Mellitus

Wagner

Kavanagh²,

Ward³

et al. 2006

ILAR Journal

159

153

View full text Add to dashboard Cite

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“…Furthermore, a number of studies have used captive nonhuman primates to investigate basic metabolic processes (Cai et al, 2004; Comuzzie et al, 2003; Hansen et al, 2013); the physiological consequences of the consumption of a particular diet (Adams et al, 2008; Bremer et al, 2011; Brozinick et al, 2013; Fabbrini et al, 2013; Kaplan et al, 2002; Nygaard et al, 2013; Stanhope et al, 2013; Sullivan et al, 2005); and the potential benefits of caloric restriction (Mattison et al, 2005; Mattison et al, 2003) on metabolic health or on changes in biomarkers that are predictive of adverse health outcomes in people. These studies are particularly informative when measures of actual calories consumed are reported (e.g., (Sullivan et al, 2005)).…”

Section: Gaps In Understanding Feeding Behavior In Nonhuman Primatesmentioning

confidence: 99%

Understanding the control of ingestive behavior in primates

Wilson

Moore

Ethun

et al. 2014

Hormones and Behavior

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Ingestive behavior in free-ranging populations of nonhuman primates is influenced by resource availability and social group organization and provides valuable insight on the evolution of ecologically adaptive behaviors and physiological systems. As captive populations were established, questions regarding proximate mechanisms that regulate food intake in these animals could be more easily be addressed. The availability of these captive populations has lead to the use of selected species to understand appetite control or metabolic physiology in humans. Recognizing the difficulty of quantitating food intake in free ranging groups, the use of captive, singly-housed animals provided a distinct advantage though, at the same time, produced a different social ecology from the animals’ natural habitat. However, with the recent application of novel technologies to quantitate caloric intake and energy expenditure in free feeding, socially-housed monkeys permits prospective studies that can accurately define how food intake changes in response to any number of interventions in the context of a social environment. This review provides an overview of studies examining food intake using captive nonhuman primates organized into three areas: a) neurochemical regulation of food intake in nonhuman primates; b) whether exposure to specific diets during key developmental periods program differences in diet preferences or changes the expression of feeding related neuropeptides; and c) how psychosocial factors influence appetite regulation. Because feeding patterns are driven by more than just satiety and orexigenic signals, appreciating how the social context influences pattern of feeding in nonhuman primates may be quite informative for understanding the biological complexity of feeding in humans.

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“…The sequences of specific genes and the arrangements of genetic loci on chromosomes reflect the close evolutionary relationship between these two species (9). Not surprisingly, nonhuman primates develop many diseases similar to those in man, and they have been used as a model for osteoporosis, lipoprotein, and atherosclerosis research (10 -12) and most recently, to study the genetics of obesity (4,13).…”

mentioning

confidence: 99%

Physiological and Molecular Determinants of Insulin Action in the Baboon

et al. 2008

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OBJECTIVE-To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/ molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance.RESEARCH DESIGN AND METHODS-Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-kinase, Akt, and AS160) were sequenced, and insulin-mediated changes were analyzed.RESULTS-Overall, baboons show a wide range of insulin sensitivity (6.2 Ϯ 4.8 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ), and there is a strong inverse correlation between indexes of adiposity and insulin sensitivity (r ϭ Ϫ0.946, P Ͻ 0.001 for % body fat; r ϭ Ϫ0.72, P Ͻ 0.001 for waist circumference). The genes and protein sequences analyzed were found to have ϳ98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulinresistant compared with lean insulin-sensitive baboons. CONCLUSIONS-The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes. Diabetes 57:899-908, 2008 I nsulin resistance is characterized by impaired response of target organs (e.g., skeletal muscle, liver, adipose tissue, and heart) to the physiological effects of insulin and results in impaired glucose metabolism. Insulin resistance is a characteristic feature of many common metabolic disorders, including obesity, type 2 diabetes, hypertension, and dyslipidemia, and of the normal aging process, which collectively constitute risk factors for the development of atherosclerotic cardiovascular disease (1-3).Nonhuman primates occupy a unique place in biomedical and evolutionary research by virtue of their close genetic and physiological similarity to humans and represent a valuable model that has great relevance to the study of human disease. Old World monkeys, which recently (ϳ25 millions years ago in evolutionary terms) diverged from the Hominoidea, have been most extensively studied (4,5). This taxonomic group includes vervet monkeys (Chlorocebus aethiops), rhesus macaques (Macaca mulatta), cynomolgus monkeys (Macaca fascicularis), and baboons (Papio hamadryas) (6). Despite the relevance of primate study to human disease research, there has been a shortage of primates available for biomedical research (7). Baboons and humans share great genetic similarity, with ϳ96% homology evident at the DNA level (8). The sequences of specific genes and the arrangements of genetic loci on chromosomes reflect the close evolutionary relationship between these two species (9). Not surprisingly, nonhuman primates develop many diseases similar to those in man, and they have been used as a model for osteoporos...

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Pleiotropic Effects of Genes for Insulin Resistance on Adiposity in Baboons

Cited by 33 publications

References 36 publications

Old World Nonhuman Primate Models of Type 2 Diabetes Mellitus

Old World Nonhuman Primate Models of Type 2 Diabetes Mellitus

Understanding the control of ingestive behavior in primates

Physiological and Molecular Determinants of Insulin Action in the Baboon

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