MAJOR NPRC GOALS IN RESEARCH ON

1
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

2
Fatty streaks and fibrous plaques in arteries of
a baboon fed a human-like atherogenic diet for 2
years.
3
Tube formation in culture by endothelial
progenitor cells derived from baboon blood.
4
PRIMATE MODELS FOR OBESITY AND DIABETES RESEARCH
Rhesus macaque
Baboon
5
BABOONS ON A NORMAL DIET DISPLAY A RANGE OF
WEIGHTS FROM LEAN TO OBESE
Males
Females
Mean weight 19.6 kg Mean age 14.3 yrs
Mean weight 30.9 kg Mean age 12.5 yrs
Weight (kg)
Weight (kg)
6
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
7
THE UNIQUE CYTOARCHITECTURE OF HUMAN PANCREATIC
ISLETS HAS IMPLICATIONS FOR ISLET CELL FUNCTION
Cabrera, O. et al., PNAS 1032334-2339, 2006.
Ca2 responses of ß cells in whole islets to
glucose
human (non-synchronized)
mouse (synchronized)
8
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.
9
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

10
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

11
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

12
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)

13
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

14
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