Splanchnic region comprises the interaction of multiple organs,
hormones and neural factors and is a critical regulator of
glucose homeostasis during both postabsorptive and absorptive
states. While splanchnic functions deteriorate during
long-standing obesity predisposing to impaired glucose regulation
and type 2 diabetes, many of the aspects of splanchnic metabolism
and blood flow (BF) in health and disease are still unknown.



In the present work, validation of positron emission
tomography (PET) for the measurement of pancreatic and intestinal
metabolism and BF in vivo was carried out and thereafter the method
was applied to a total of 62 morbidly obese and 40 healthy
individuals. In a set of cross-sectional and longitudinal studies
glycemic control and β-cell function, splanchnic glucose and lipid
metabolism, and splanchnic vascular responses to a mixed-meal, incretin
infusions and glucose loading were explored before and after
bariatric surgery and weight loss.



Compared to healthy controls, pancreatic fatty acid (FA)
uptake and steatosis were markedly increased in obese patients
whereas pancreatic glucose uptake (GU) and BF were impaired. Elevated
pancreatic steatosis and inadequate BF were associated with poor
insulin secretion rate. In the small intestine, insulin upregulated GU
nearly three-fold over the fasting values in healthy controls
whereas normally glucose tolerant obese patients were unresponsive
to the stimulatory effect of insulin. In lean controls and patients with
type 2 diabetes, mixed-meal increased both pancreatic and
intestinal BF, whereas GIP infusion decreased and increased
pancreatic and intestinal BF, respectively. Bariatric surgery was
followed by a prominent weight loss, increase in insulin sensitivity and
β-cell function, and decrease in pancreatic FA uptake, rate of
steatosis and BF. While the vascular responses of GIP were
essentially similar at post-surgery when compared to pre-surgery,
splanchnic vascular responses during mixed-meal were enchanced,
likely as a result of rapid gastric emptying.



In conclusion, pancreatic and small intestinal metabolism and
BF respond to obesity and type 2 diabetes, and to metabolic changes
elicited by bariatric surgery. The adequacy of pancreatic BF responses
and insulin-dependence of intestinal GU are pivotal concepts in the
regulation of glucose homeostasis in humans. Obesity influences
both of these physiological concepts, whereas altered gastrointestinal
anatomy, incretins responses and weight loss after bariatric surgery
are able to reverse these obesity-induced perturbations leading to
improved glucose homeostasis.