The autonomic nervous system, made up of sympathetic and parasympathetic branches, is known to regulate blood glucose levels by directly controlling insulin secretion by the pancreas. Insulin secretion and blood glucose levels are also regulated by hormonal factors such as leptin. Despite the critical role of the autonomic nervous system in the regulation of islet hormone secretion, little is known about the mechanisms involved in the development of the autonomic innervation of the pancreas. Now, a study led by researchers at The Children’s Hospital Los Angeles (CHLA) shows that the presence of leptin during embryonic development inhibits the development of neuronal connections between the brain and pancreas. The team state that their findings could help explain the origin of type 2 diabetes, particularly in children of obese mothers. The opensource study is published the journal Cell Reports.
Previous studies show that the parasympathetic fibers that innervate the endocrine pancreas originate primarily from neurons in the intrapancreatic ganglia. In contrast, sympathetic fibers within in the pancreas originate from preganglionic cell bodies that are located in the thoracic and upper lumbar segments of the spinal cord. Both the parasympathetic and sympathetic systems develop before birth, and autonomic nerve fibers can be observed in various peripheral organs as early as mid-gestation. In addition, pancreatic function is also regulated by hormonal factors, including leptin which has been shown to influence sympathetic tone and glucose homeostasis. The effects of leptin are controlled by neurons located in both the hypothalamus and hindbrain. In addition to the physiological effects it exerts during adult life, leptin provides support to hypothalamic neural projections during development. However, whether leptin influences the development of non-hypothalamic circuits remains unknown. The current study identifies a regulatory role for leptin on the parasympathetic nervous system during embryonic development, which may have important implications for understanding the early mechanisms that contribute to diabetes.
The current study shows that exposure of the embryonic mouse brain to leptin during a key developmental period resulted in permanent alternations in the growth of neurons between the brain stem to the pancreas, resulting in long-term disturbances to the balance of insulin levels in the adult mouse.
Results show that leptin receptors are highly expressed in the brain stem when autonomic innervation occurs, creating direct connections between the brain and pancreatic β cells, and the factors influencing it during embryonic development. Data findings show that when a single dose of leptin was injected into the brain of mouse embryos during mid-gestation, it had a permanent effect of reducing connectivity between the brain stem and pancreas.
The team surmise that their findings ultimately show a breakdown in communication between the brain and the pancreas results in impaired glucose regulation, or homeostasis, in the adult mouse. They go on to add that their study identifies an unanticipated regulatory role for the leptin hormone known to be produced by fat cells. For the future, the researchers state that because babies of obese moms have high levels of leptin, it might put them at a higher risk for type 2 diabetes and obesity.
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