# Presentation: 137002

## MAJOR NPRC GOALS IN RESEARCH ON

**HEART DISEASE, DIABETES, AND OBESITY**

- To develop naturally occurring and experimentally induced models in nonhuman primates
- To use them to determine the biological mechanisms that lead to these diseases
- To understand the genetic and environmental factors that influence disease onset and progression
- To translate results into new strategies for prevention and treatment

## Fatty streaks and fibrous plaques in arteries of a baboon fed a human-like atherogenic diet for 2 years.

## Tube formation in culture by endothelial progenitor cells derived from baboon blood.

## PRIMATE MODELS FOR OBESITY AND DIABETES RESEARCH

**PRIMATE MODELS FOR OBESITY AND DIABETES RESEARCH**

**Rhesus macaque**

**Baboon**

## BABOONS ON A NORMAL DIET DISPLAY A RANGE OF WEIGHTS FROM LEAN TO OBESE

**Mean weight = 19.6 kg**
**Mean age = 14.3 yrs**

**Mean weight = 30.9 kg**
**Mean age = 12.5 yrs**

**Weight (kg)**

**Weight (kg)**

**Females**

**Males**

## BABOONS ALSO EXHIBIT HYPERGLYCEMIA AND HYPERINSULINEMIA

**BABOONS ALSO EXHIBIT HYPERGLYCEMIA AND HYPERINSULINEMIA**

**Elevated fasting blood glucose:**
**symptom of pre-diabetes**

**Elevated fasting insulin:**
**symptom of progression to**
**frank type-2 diabetes**

## THE UNIQUE CYTOARCHITECTURE OF HUMAN PANCREATIC ISLETS HAS IMPLICATIONS FOR ISLET CELL FUNCTION

**THE UNIQUE CYTOARCHITECTURE OF HUMAN PANCREATIC ISLETS HAS IMPLICATIONS FOR ISLET CELL FUNCTION**

***Cabrera, O. et al., PNAS 103:2334-2339, 2006.***

**[Ca****2+****] responses of ****β**** cells in whole islets to glucose**

**human (non-synchronized)**

**mouse (synchronized)**

## ACTIVE NIH GRANTS

**EMPLOYING PRIMATES**
- (CRISP DATABASE SEARCH, 28 NOVEMBER 2007)

- Heart or Cardiovascular Disease or Atherosclerosis	35
- Hypertension or Blood Pressure				12
- Diabetes or Metabolic Syndrome				33
- Obesity							11
**Total**								871
- 114 grants appear in two groups, so there are 73 unique active grants.

## REPRESENTATIVE NIH-FUNDED PROJECTS USING BABOONS AT NPRCs	

**Diet and Genotype in Primate Atherosclerosis, P01 HL028972**
- discovering genes that affect physiologic risk factors of athersclerosis, diabetes, and obesity using pedigreed, genotyped baboons, and determining dietary effects on expression of those genes
- discovering genes that affect numbers of circulating endothelial progenitor cells at baseline and after arterial injury

## REPRESENTATIVE NIH-FUNDED PROJECTS USING BABOONS AT NPRCs	

**Diet and Genotype in Primate Atherosclerosis, P01 HL028972**
- discovering genes that affect physiologic risk factors of athersclerosis, diabetes, and obesity using pedigreed, genotyped baboons, and determining dietary effects on expression of those genes
- discovering genes that affect numbers of circulating endothelial progenitor cells at baseline and after arterial injury

**Angiotensin, Sodium and Genes in Primate Hypertension, R01 HL068180**
- determining genetically controlled mechanisms that lead to hypertension in pedigreed, genotyped baboons

## REPRESENTATIVE NIH-FUNDED PROJECTS USING BABOONS AT NPRCs	

**Diet and Genotype in Primate Atherosclerosis, P01 HL028972**
- discovering genes that affect physiologic risk factors of athersclerosis, diabetes, and obesity using pedigreed, genotyped baboons, and determining dietary effects on expression of those genes
- discovering genes that affect numbers of circulating endothelial progenitor cells at baseline and after arterial injury

**Angiotensin, Sodium and Genes in Primate Hypertension, R01 HL068180**
- determining genetically controlled mechanisms that lead to hypertension in pedigreed, genotyped baboons

**Novel Therapy for Diabetes, R01 DK069037**
- developing experimental diabetic baboon model by treating with streptozotocin
- moving from the mouse to the baboon model to test gene therapy to induce islet neogenesis

## REPRESENTATIVE NIH-FUNDED PROJECTS USING RHESUS MONKEYS OR 

**MARMOSETS AT NPRCs****	**

**Pathobiology and Gene Transfer in Cardiovascular Disease, P01 HL059214**
- developing improved adenovirus vectors for gene therapy applications
- testing vectors carrying the LDL receptor gene in rhesus monkeys with a genetically defective LDL receptor gene (cause of Familial Hypercholesterolemia)

## REPRESENTATIVE NIH-FUNDED PROJECTS USING RHESUS MONKEYS OR 

**MARMOSETS AT NPRCs****	**

**Pathobiology and Gene Transfer in Cardiovascular Disease, P01 HL059214**
- developing improved adenovirus vectors for gene therapy applications
- testing vectors carrying the LDL receptor gene in rhesus monkeys with a genetically defective LDL receptor gene (cause of Familial Hypercholesterolemia)

**Effect of Fish Oil and Alpha Lipoic Acid on the Progression of Insulin Resistance, R21 AT003645**
- identifying mechanisms by which dietary supplements may reduce rate of progression of Metabolic Syndrome

## REPRESENTATIVE NIH-FUNDED PROJECTS USING RHESUS MONKEYS OR 

**MARMOSETS AT NPRCs****	**

**Pathobiology and Gene Transfer in Cardiovascular Disease, P01 HL059214**
- developing improved adenovirus vectors for gene therapy applications
- testing vectors carrying the LDL receptor gene in rhesus monkeys with a genetically defective LDL receptor gene (cause of Familial Hypercholesterolemia)

**Effect of Fish Oil and Alpha Lipoic Acid on the Progression of Insulin Resistance, R21 AT003645**
- identifying mechanisms by which dietary supplements may reduce rate of progression of Metabolic Syndrome

**The Common Marmoset as a Primate Model of Maternal Obesity, **
**R01 DK077639**
- determining the effects of maternal obesity on development of obesity and diabetes in progeny after they reach adulthood