GASTRIC BYPASS: ITS ROLE IN TREATING DIABETES IS MORE THAN JUST FORCED FOOD INTAKE REDUCTION
Bariatric surgery is an extreme procedure involving gastric
bypass as a means of treatment for morbid obesity and obesity. There are many
different types of gastric bypass with the Roux-en-Y procedure (RYGB) being one
of the more common. The RYGB procedure involves surgically reducing the size of
the stomach to a small pouch by stapling off a section of the stomach then attaching
this pouch directly to the small intestine, bypassing most of the rest of the
stomach and the upper part of the small intestine. RYGB has been shown to
induce substantial and sustained weight loss. An interesting and unexpected
finding in patients who underwent the RYGB is that the observed improvement in overall
glucose homeostasis occurs early after the RYGB procedure, before any appreciable
weight loss, and as a result these patients are often able to discontinue their
antidiabetic medications before hospital discharge. However, the means by which
the RYGB effected these changes in glucose homeostasis have not been determined.
In a recent study published in the prestigious journal
Science it has been determined that a major metabolic consequence of the RYGB procedure
is an increase in glucose utilization by the intestines resulting in increased
disposal of glucose from the blood, thereby, rapidly reducing the hyperglycemia
of type 2 diabetes.
The authors of this study hypothesized that that the beneficial
effect of RYGB on glucose homeostasis might likely be due to the fact that the
jejunum (the middle section of the small intestine), which normally does not
see undigested food, now has an altered metabolism necessary to meet the
increased bioenergetic demands of tissue growth and maintenance, possibly in
response to exposure of this section of the intestine to undigested nutrients.
These studies were carried out in rats and the initial work
centered on a comparative analysis of the metabolic profiles in sham operated
jejunal tissue versus RYGB jejunal tissue. The results of metabolomic profiling
showed increased concentrations of intermediates of the oxidative phase of the
pentose phosphate pathway, increased intermediates of the pyrimidine and purine
biosynthetic path-ways, increased lactate production was increased, there was increased
serine biosynthesis and hexosamine biosynthetic activity, two
metabolic pathways that branch off from glycolysis. In addition, the glutamine/glutamate
pathway was enhanced as was the metabolism of several other amino acids. The
observed changes in metabolic profiles following the RYGB indicates that
glycolysis may be up-regulated in in order to shunt glucose carbons into metabolic
pathways that support the accumulation of biomass necessary for cellular growth
and proliferation. Metabolomic changes in the RYGB rats were also mirrored by
examination of transcriptomic profiles that demonstrated increased expression
of key glycolytic enzymes.
The effectiveness of RYGB, not only at the level of weight
loss, but in the resolution of hyperglycemia and insulin resistance in type 2
diabetes attests to the important role of the gastrointestinal tract in overall
glucose homeostasis. Most previous studies suggested that these effects of RYGB
were due to changes gastrointestinal hormones that control glucose homeostasis such
as glucagon-like peptide-1 (GLP-1). Other animal studies have also demonstrated
that changes in intestinal gluconeogenesis following a different type of gastric
bypass resulted in reduced hepatic gluconeogenesis. However, studies in humans
who underwent the RYGB procedure did not show appreciable induction of
intestinal gluconeogenesis so there is some controversy as to the role of
intestinal gluconeogenesis in the efficacy of gastric bypass in ameliorating
the hyperglycemia of type 2 diabetes.
The TAKE HOME from this study first confirms the
physiological benefits of the use of the RYGB procedure in the treatment of
obesity and type 2 diabetes. Specifically, this study demonstrated that changes
in overall metabolism in the jejunal limb of the bypass structure may be
primarily responsible for improved glucose homeostasis following RYGB. The
resulting reprogrammed intestinal glucose metabolism leads to the intestine becoming
a major organ for glucose disposal which in turn contributes to the overall improvement
in glycemic control following RYGB and the associated improvement in the hyperglycemia associated with type 2 diabetes.
Comments
Post a Comment