Presence of Hormone at Key Developmental Period May Point to Origin of Type 2 Diabetes in Kids

LOS ANGELES–(BUSINESS WIRE)–A new study led by researchers at The Saban Research Institute of
Children’s Hospital Los Angeles (CHLA) reports that the presence of
leptin – a hormone secreted by fat cells that is critical to maintaining
energy balance in the body — inhibits the prenatal development of
neuronal connections between the brain and pancreas. The findings could
help explain the origin of type 2 diabetes, particularly in children of
obese mothers.


This study reveals an unanticipated regulatory role of leptin on the
parasympathetic nervous system during embryonic development, which may
have important implications for understanding the early mechanisms that
contribute to diabetes. The findings will be published online by the
journal Cell Reports on March 24 in advance of print publication on
April 5.

The autonomic nervous system, made up of sympathetic and parasympathetic
branches, is essential for the regulation of blood glucose levels by
directly controlling insulin secretion by the pancreas. Insulin
secretion and blood glucose levels are also regulated by hormonal
factors, including leptin, and dysregulation of pancreatic function and
insulin secretion is a hallmark of diabetes.

“We showed that exposure of the embryonic mouse brain to leptin during a
key developmental period resulted in permanent alternations in the
growth of neurons from the brain stem to the pancreas, resulting in
long-term disturbances to the balance of insulin levels in the adult
mouse,” said Sebastien G. Bouret, PhD, researcher in the developmental
neuroscience program at CHLA.

Looking at when autonomic innervation occurred – creating direct
connections between the brain and pancreatic β cells – and the factors
influencing it during embryonic development, the scientists found that
leptin receptors are highly expressed in the brain stem. When the
scientists injected a single dose of leptin directly into the brain of
mouse embryos during mid-gestation, it had a permanent effect of
reducing connectivity between brain stem and pancreas.

“This breakdown in communication from the brain to the pancreas resulted
in impaired glucose regulation, or homeostasis, in the adult mouse,”
said Bouret, who is also an associate professor of pediatrics at the
Keck School of Medicine of the University of Southern California. “This
study reveals an unanticipated regulatory role for the leptin hormone
known to be produced by fat cells. Because babies of obese moms have
high levels of leptin, it might put them at a higher risk for type 2
diabetes and obesity.”

Additional contributors to the study include first author Sophie
Croizier of Children’s Hospital Los Angeles, and Vincent Prevot of
Inserm, Jean-Pierre Aubert Research Center, Lille, France. The work was
supported in part by grants from the National Institutes of Health
(DK84142, DK102780, and P01ES022845) and the United States Environmental
Protection Agency.

About Children’s Hospital Los Angeles

Children’s Hospital Los Angeles has been named the best children’s
hospital in California and among the top 10 in the nation for clinical
excellence with its selection to the prestigious U.S. News & World
Report Honor Roll. Children’s Hospital is home to The Saban Research
Institute, one of the largest and most productive pediatric research
facilities in the United States. Children’s Hospital is also one of
America’s premier teaching hospitals through its affiliation since 1932
with the Keck School of Medicine of the University of Southern
California. For more information, visit CHLA.org.
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Contacts

Children’s Hospital Los Angeles
Debra Kain
323-361-7628 or
323-361-1812
dkain@chla.usc.edu