Glucose metabolism and pancreatic defects in spinal muscular atrophy
M Bowerman, KJ Swoboda, JP Michalski… - Annals of …, 2012 - Wiley Online Library
M Bowerman, KJ Swoboda, JP Michalski, GS Wang, C Reeks, A Beauvais, K Murphy…
Annals of neurology, 2012•Wiley Online LibraryObjective: Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It
is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although
SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic
acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been
reported in SMA patients. We thus initiated an in‐depth analysis of glucose metabolism in
SMA. Methods: Glucose metabolism and pancreas development were investigated in the …
is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although
SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic
acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been
reported in SMA patients. We thus initiated an in‐depth analysis of glucose metabolism in
SMA. Methods: Glucose metabolism and pancreas development were investigated in the …
Objective
Spinal muscular atrophy (SMA) is the number 1 genetic killer of young children. It is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Although SMA is primarily a motor neuron disease, metabolism abnormalities such as metabolic acidosis, abnormal fatty acid metabolism, hyperlipidemia, and hyperglycemia have been reported in SMA patients. We thus initiated an in‐depth analysis of glucose metabolism in SMA.
Methods
Glucose metabolism and pancreas development were investigated in the Smn2B/− intermediate SMA mouse model and type I SMA patients.
Results
Here, we demonstrate in an SMA mouse model a dramatic cell fate imbalance within pancreatic islets, with a predominance of glucagon‐producing α cells at the expense of insulin‐producing β cells. These SMA mice display fasting hyperglycemia, hyperglucagonemia, and glucose resistance. We demonstrate similar abnormalities in pancreatic islets from deceased children with the severe infantile form of SMA in association with supportive evidence of glucose intolerance in at least a subset of such children.
Interpretation
Our results indicate that defects in glucose metabolism may play an important contributory role in SMA pathogenesis. ANN NEUROL 2012;72:256–268.
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