As peripheral glucose uptake increases (upper trace), liver glucose output decreases (lower trace). The half-times are about the same (vertical arrows) suggesting a common rate-limiting step. Diabetes 93
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My graduate research was about endocrinology and metabolism. I first studied hormonal control of fat deposition with Dr. Harvey Kaslow. I developed a mathematical model to measure fatty acid uptake in adipocytes using radioactive tracers.
Next I studied endocrine control of glucose production in the laboratory of Dr. Richard Bergman. We first developed a pancreatic clamping technique to measure glucagon sensitivity for the first time in vivo. We then used the technique, along with a mathematical model of glucose distribution, to produce the first accurate measurement of liver glucose output. Under these conditions, we studied the time course of insulin's effect to suppress glucose output. The results contradicted all previous studies by showing a very slow time course. Remarkably, the time course was precisely the same as the time course for the stimulation of peripheral glucose uptake by insulin. The rather startling conclusion was that insulin's liver effect is probably mediated by a second messenger generated in the periphery. Subsequent work in the Bergman lab revealed that this second messenger is probably fatty acid. For more details, see Bradley et al, Diabetes 93 and Bergman et al, AEMB 93.
Reiterative algorithm for the adaptive smoothing technique. CMPB 95
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Finally, we developed a statistical algorithm for smoothing time course data for plasma metabolites. Other smoothing techniques had been around but all required the investigator to adjust the smoothness, creating an inescapable bias. Our method smooths repetitively, in each case examining the residuals for statistical randomoness. The algorithm converges when the residuals are free of serial correlation. Under such conditions the remaining (smoothed) data contain no more or less than the information-bearing component of the data. For more information see Bradley et al, AJP 93 and Bradley et al, CMPB 95.
Diabetes & Metabolism: Papers
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