Splanchnic Metabolism and Blood Flow In Man. PET Studies with Reference to Obesity and Diabetes
Year: 2016
Type: dissertation
Study design: Observational Study
Abstract: 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.
Source: UTUPub (University of Turku)
Author: Henri Honka
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2556915470