Diet-induced obesity and pancreatic islet blood flow in the rat: a preferential increase in islet blood perfusion persists after withdrawal of the diet and normalization of body weight

Abstract

The aim of the present study was to evaluate the effects of diet-induced obesity on pancreatic islet blood perfusion in normal Wistar rats. Furthermore, we investigated to what extent any obesity-associated changes in islet blood flow could be reversed after reversion to a normal diet with normalization of body weight. Young adult female Wistar rats were offered a palatable mixed high-caloric diet (cafeteria diet) in addition to standard pelleted chow. Age-matched control rats received standard pelleted chow only. After 4 weeks the diet-treated rats had a body weight of approximately 15% more than that of the controls. All diet-treated rats had decreased glucose tolerance and increased serum insulin concentrations, but basal blood glucose concentrations were similar in anesthetized diet-treated and control rats. Whole pancreatic and islet blood flow rates were measured with a microsphere technique. The islet blood flow as well as fractional islet blood flow were increased (P < 0.01) in rats fed the cafeteria diet, while blood perfusion of the whole pancreas was similar to that of the control rats. In a second experiment, rats received the cafeteria diet for 4 weeks and were then fed standard pelleted food alone for another 3 weeks, while controls received standard diet for 7 weeks. After this period total body weight, retroperitoneal fat pad weight and glucose tolerance were similar to those of the controls. Whole pancreatic blood flow was unchanged as compared with that of control rats. However, both islet blood flow (P < 0.01) and fractional blood flow (P < 0.01) were increased. We conclude that diet-induced obesity in rats is associated with decreased glucose tolerance, hyperinsulinemia and a specific increase in absolute and fractional islet blood perfusion. This increase persists for at least 3 weeks after the diet is withdrawn despite normalization of body weight and glucose tolerance.

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

“…Thus, the islet blood flow in partially pancreatectomized Wistar rats increased to such a magnitude that the total blood perfusion to islets in these rats reached the same level as the islet blood flow in the whole pancreas in the sham-operated animals. This finding confirms previous observations linking augmented islet blood flow to settings with increased need for insulin secretion (see Jansson & Sandler 1989, Styrud et al 1992, Atef et al 1992, 1994, Svensson et al 1996. Obviously, increased islet blood flow could constitute one mechanism for maintaining normal glucose homeostasis in the face of increased functional demand, i.e.…”

“…We have previously noted a decrease in islet blood flow 1 week after intra-abdominal sham operations in Sprague-Dawley rats (Jansson & Andersson 1997), which may reflect responses to changes in abdominal pressure or inflammatory reactions following laparotomy. GK and hybrid rats may be more sensitive to such events, in line with our previous observations that vagotomy and treatment with atropine decreases islet blood flow in hybrid rats to levels similar to those of normal Wistar rats (Svensson et al 1996).…”

“…This suggests that whereas normal rats may compensate for the surgical removal of endocrine tissue by regeneration and hyperperfusion of the islets, these mechanisms are much less efficient, or even absent, in GK rats. It is of interest that a similar decrease in islet blood flow is seen in aging GK rats, which have an even more impaired glucose tolerance (Svensson et al 2000). The present findings lend support to the notion that, in this model, a decrease in islet blood flow may precede the functional impairment of the islets.…”

“…A number of possibly interdependent neural and local factors have been suggested to influence islet blood perfusion (Jansson 1994, Brunicardi et al 1996. Our earlier investigations have pointed to an association between increased functional load on the islets and increased islet blood flow in different experimental systems, namely 48 h continuous highglucose load, partial pancreatectomy and diet-induced and inherited obesity (Jansson & Sandler 1989, Styrud et al 1992, Jansson 1994, Svensson et al 1996. Although the mechanisms underlying these aberrations remain obscure, it could be envisaged that increased islet blood flow is a compensatory mechanism that may contribute to increased hormone output.…”

Pancreatic islet blood flow during pregnancy in the rat: an increased islet mass is associated with decreased islet blood flow

“…increased peripheral insulin resistance (Atef et al 1994). Islet blood flow is also increased in animal models of type 2 diabetes, such as GK rats (Svensson et al 1994a(Svensson et al , 1996, obese Zucker rats (Atef et al 1992) and obese-hyperglycemic mice (Carlsson et al 1996). We, and others, have previously suggested that changes in islet blood flow may influence hormone release from the islets (Jansson 1994, Moldovan et al 1996, and provide partial compensation for insufficient insulin release.…”