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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Blood Glucose, Diabetes Mellitus, Experimental, Gene Transfer Techniques, Genetic Therapy, Insulin, Male, Mice, Mice, Inbred BALB C, Muscle, Skeletal, Plasmids, Proinsulin, Rats.
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Does naked plasmid-mediated gene transfer to skeletal muscle ameliorate diabetes mellitus? Context: The ability of tissues to take up naked plasmid DNA in vivo suggests an approach for reconstituting systemic metabolic deficiencies without the disadvantages of viral vectors and lipid-DNA complexes. Plasmid-mediated gene transfer into skeletal muscle was investigated as a means of providing a therapeutic source of insulin. Four plasmid constructs, each bearing a mouse furin cDNA transgene and rat proinsulin cDNA (modified for processing by furin) driven by four different promoters were injected into the calf muscles of male Balb/c mice. Insulin and C-peptide concentrations were measured by radio-immunoassays having minimal crossreactivity for proinsulin and partially processed proinsulin. Intramuscular insulin concentrations increased by up to 3.6-fold over controls seven days after single injections of CMV, beta-actin, hsp70 and myoglobin promoter constructs. The optimal dose for most constructs was 100 micrograms plasmid DNA. Intramuscular plasmid injection into streptozotocin-induced diabetic Balb/c mice raised plasma insulin and C-peptide concentrations, and reduced hyperglycaemia. Two injections (100 micrograms plasmid DNA each) caused higher plasma insulin concentrations and significantly reduced hyperglycemia in diabetic mice than a single injection. Best results were obtained when plasmid injections preceded induction of diabetes by 14 days.
assistant
Skeletal muscle is a potentially useful platform for ectopic secretion of insulin using naked plasmid as a gene transfer vector. Injection at two sites 14 days before the onset of severe hyperglycemia is optimal. This approach could protect Type I diabetics from fatal ketoacidosis and enhance the action of agents that sensitize tissues to insulin in type II diabetes. Final Decision: yes