Comparison of Superior Mesenteric Versus Jugular Venous Infusions of Insulin in Streptozotocin-Diabetic Rats on the Choice of Caloric Intake, Body Weight, and Fat Stores

Abstract

Corticosterone (B) increases and insulin decreases food intake. However, in streptozotocin (STZ)-diabetic rats with high B, low insulin replacement promotes lard intake. To test the role of the liver on this, rats were given STZ and infused with insulin or vehicle into either the superior mesenteric or right jugular vein. Controls were nondiabetic; all rats were treated with high B. After 5 d, all rats were offered lard, 32% sucrose, chow, and water ad libitum until d 10. Diabetes exacerbated body weight loss from high B; this was prevented by insulin into the jugular, but not superior mesenteric, vein. Without insulin, STZ groups essentially consumed only chow; controls increased caloric intake about equally from the three sources. Insulin into both sites reduced chow and increased lard intake. Although circulating insulin was increased only by jugular infusion, plasma glucose and liver glycogen were similar after insulin into both sites. Fat depot weights differed: sc fat was heavier after jugular and mesenteric fat was heavier after mesenteric insulin infusions. We conclude that there are important site-specific effects of insulin in regulating the choice of, but not total, caloric intake, body weight, and fat storage in diabetic rats with high B. Furthermore, lard intake might be regulated by an insulin-derived, liver-mediated signal because superior mesenteric insulin infusion had similar effects on lard intake to jugular infusion but did not result in elevated circulating insulin levels likely associated with liver insulin removal.

The gastroduodenal branch of the common hepatic vagus regulates voluntary lard intake, fat deposition, and plasma metabolites in streptozotocin-diabetic rats

“…In the rat model utilized in the main experiment, plasma corticosterone was maintained at steady-state levels that correspond to near-circadian maximum concentrations (1), which stimulates lard intake (26). Voluntary lard intake was further manipulated by treatment with STZ, which reduces intake (26,56). Thus, these manipulations produce a spectrum of lard intake that is insulin sensitive and is of a magnitude sufficient to reveal the effects of our experimental manipulations.…”

“…also controls for any STZ-induced changes in corticosterone levels (46,47) that would confound interpretation of the effects of insulin and GV on food intake. The superior mesenteric vein was chosen as the site of venous insulin treatment, as infusion from this location is similar to the ordinary path of insulin from the pancreas and has been shown (54,56) to robustly promote lard intake. The dose of 3 U insulin/day was selected since it reliably promotes lard intake and can produce detectable changes in plasma insulin and liver glycogen levels in STZ-diabetic rats (54,56).…”

“…The superior mesenteric vein was chosen as the site of venous insulin treatment, as infusion from this location is similar to the ordinary path of insulin from the pancreas and has been shown (54,56) to robustly promote lard intake. The dose of 3 U insulin/day was selected since it reliably promotes lard intake and can produce detectable changes in plasma insulin and liver glycogen levels in STZ-diabetic rats (54,56). It was not necessary for this dose to control the diabetes but only to facilitate lard intake, since glucose has been indirectly precluded in our other studies (26,56) as the insulin-sensitive signal that regulates lard intake.…”

“…The dose of 3 U insulin/day was selected since it reliably promotes lard intake and can produce detectable changes in plasma insulin and liver glycogen levels in STZ-diabetic rats (54,56). It was not necessary for this dose to control the diabetes but only to facilitate lard intake, since glucose has been indirectly precluded in our other studies (26,56) as the insulin-sensitive signal that regulates lard intake.…”

“…Specifically for insulin, streptozotocin (STZ)-induced insulin-dependent diabetes reduces lard intake to favor chow, a situation that is reversed by exogenous insulin treatment (26,54,56). STZ-diabetes also results in behavioral, autonomic, endocrine, and neuroendocrine characteristics of chronic stress in rodents (47).…”