Biology Reference
In-Depth Information
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Figure 3
Time course of muscle glycogen concentration calculated from the
13
C MRS
spectra during an insulin and glucose infusion for noninsulin-dependent diabetes mellitus
subjects and healthy controls.
The subjects with diabetes (solid symbols) synthesize glycogen slower than the control subjects
(open symbols). Quantitation of the rates showed that insulin-stimulated glycogen synthesis is the
major metabolic pathway of glucose disposal in both groups and that the impairment in muscle
glycogen synthesis accounts for the reduced glucose disposal in the subjects with type 2 diabetes.
(Reprinted from
Metabolomics by
In Vivo
NMR
(eds Shulman RG and Rothman DL) copyright
Wiley, England, 2005.)
showed that the flux was controlled by recruitment of glucose transporters to the
plasma membrane, thereby controlling the flux of glycogenesis. This recruitment
was less responsive to insulin in the diabetic subjects and was responsible for
the slower clearance of glucose, which created the disease. The disease did
not appear until later life because in the early years the pancreas overproduced
insulin to compensate for its reduced effectiveness. Furthermore, we showed
how dietary protocols and exercise could restore normal glucose clearance rates
by normalizing this particular step. In this disease, we had found the particular
pathway whose controlling step was genetically deficient in the patients and had
shown that the deficiency worsened in response to the environmental factors of
inactivity and obesity. The large questions of nature and nurture were playing
out in a chemical pathway. We could also measure and begin to study how
the individual's contingent history affected the onset of the disease caused by
pancreatic failure. Despite the well-established environmental influence of diet
and exercise some slim, athletic subjects became ill while other overweight,
couch potatoes did not.
The research described has built upon the cumulative advances in medicine,
chemistry, and physics through the centuries. Diabetes was recognized in the
