Central GIP signaling stimulates peripheral GIP release and promotes insulin and pancreatic polypeptide secretion in nonhuman primates.

Glucose-dependent insulinotropic polypeptide (GIP) has important actions on whole body metabolic function. GIP and its receptor are also present in the central nervous system and have been linked to neurotrophic actions. Metabolic effects of central nervous system GIP signaling have not been reported. We investigated whether centrally administered GIP could increase peripheral plasma GIP concentrations and influence the metabolic response to a mixed macronutrient meal in nonhuman primates. An infusion and sampling system was developed to enable continuous intracerebroventricular (ICV) infusions with serial venous sampling in conscious nonhuman primates. Male baboons (Papio sp.) that were healthy and had normal body weights (28.9 ± 2.1 kg) were studied (n = 3). Animals were randomized to receive continuous ICV infusions of GIP (20 pmol·kg-1·h-1) or vehicle before and over the course of a 300-min mixed meal test (15 kcal/kg, 1.5g glucose/kg) on two occasions. A significant increase in plasma GIP concentration was observed under ICV GIP infusion (66.5 ± 8.0 vs. 680.6 ± 412.8 pg/ml, P = 0.04) before administration of the mixed meal. Increases in postprandial, but not fasted, insulin (P = 0.01) and pancreatic polypeptide (P = 0.04) were also observed under ICV GIP. Effects of ICV GIP on fasted or postprandial glucagon, glucose, triglyceride, and free fatty acids were not observed. Our data demonstrate that central GIP signaling can promote increased plasma GIP concentrations independent of nutrient stimulation and increase insulin and pancreatic polypeptide responses to a mixed meal.

Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

The function of prostate-specific antigen (PSA) is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR) product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes), cynomolgus monkeys (Macaca fascicularis), baboons (Papio hamadryas anubis), and African green monkeys (Chlorocebus aethiops). Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS) of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203).

Androgen receptor CAG repeat polymorphism in males of six non-human primate species.

BACKGROUND: Androgen receptor [CAG](n) microsatellite has been linked to human diseases. METHODS: Six non-human primates were genotyped for the [CAG](n) microsatellite. RESULTS: Marmosets and macaques are monomorphic, while mangabeys, baboons, and chimpanzees are polymorphic. CONCLUSIONS: Non-human primates that are polymorphic for the microsatellite are candidate animal models for CAG-related diseases.

Serum prostate specific antigen changes in cynomolgus monkeys (Macaca fascicularis) on a high sugar high fat diet.

BACKGROUND: An inverse relationship between serum prostate specific antigen (PSA) levels and body mass index (BMI) has been reported in men but not in any animal model. METHODS: Serum PSA in a colony of cynomolgus monkeys was assayed and correlated to body weight, prostate weight, and age. In addition, 15 animals were selected and fed a high sugar high fat (HSHF) diet for 49 weeks to increase their BMI and correlate it to PSA RESULTS: Serum PSA levels were positively correlated to prostate weight (r = 0.515, P = 0.025) and age (r = 0.548, P = 0.00072) but was not significantly correlated to body weight (r = -0.032, P = 0.419). For the animals on the HSHF diet, body weight, lean mass, fat mass, and BMI were significantly higher at 49 weeks than at baseline (P < 0.01). PSA was not significantly correlated to body weight and insulin at both baseline and 49 weeks. PSA was negatively correlated to BMI and insulin resistance (HOMA-IR) at 49 weeks but not at baseline. In addition, we observed hepatic steatosis and increases in serum liver enzymes. CONCLUSIONS: Increases in BMI in cynomolgus monkeys as a result of consuming a HSHF diet resulted in PSA changes similar to those in humans with increased BMI. Cynomolgus monkeys are a useful model for investigating the relationship between obesity, diabetes, and PSA changes resulting from prostate gland pathology.

A preliminary report on the feeding of cynomolgus monkeys (Macaca fascicularis) with a high-sugar high-fat diet for 33 weeks.

BACKGROUND: The metabolic syndrome is common in populations exposed to a typical Western diet. There is a lack of an animal model that mimics this condition. METHODS: We fed 15 cynomolgus monkeys ad libitum a high-sugar high-fat (HSHF) diet for 33 weeks. Body weight, body composition, serum lipids, and insulin were measured at baseline and at 33 weeks. RESULTS: The animals tolerated the HSHF diet very well. In the intervention group, total serum cholesterol and low-density lipoprotein cholesterol were 3- and 5-fold higher, respectively, at 33 weeks as compared with their baseline levels. Serum high-density lipoprotein cholesterol and triglycerides were not significantly affected. Dual-energy X-ray absorptiometry (DXA) analysis of the intervention group indicated that the trunk fat mass increased by 187% during this period. CONCLUSIONS: Cynomolgus monkeys should be a useful model for investigating the interactions of diet and other factors such as genetics in the development of the metabolic syndrome.