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PubMed1991

Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats.

Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days. Control rats were given vehicle and were fed ad libitum or pair-fed together with the rIL-1 beta treated rats. An ip glucose tolerance test (0.2 g D-glucose/100 g) was performed 2 h after injection of rIL-1 beta. A single injection of rIL-1 beta caused a mild depression in blood glucose and an improved glucose tolerance. Multiple injections of rIL-1 beta induced a diminished weight gain, a 24-28% reduction in food intake, a lasting mild depression of blood glucose (7 days) and a transiently impaired glucose tolerance on day 5. We conclude that systemic IL-1 should be considered an important regulator of glucose homeostasis in vivo.

Animals↗
PubMed1997

Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide.

The emerging view is that reduced feed intake, lean muscle accretion, and growth in immunologically challenged pigs is the result of increased cytokine activity, but this has not been directly tested. To begin addressing this issue, 72 crossbred barrows and gilts (11.55 +/- .19 kg BW) were not fed for 12 h and then injected i.p. with 0, .5, or 5 micrograms/kg of Escherichia coli lipopolysaccharide (LPS). Blood was collected by jugular puncture at 0, 2, 4, 8, 12, and 24 h after injection. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cortisol, plasma urea nitrogen (PUN), NEFA, and triglycerides were determined. Immunological stress was induced by LPS as indicated by increased secretion of TNF-alpha, IL-6, and cortisol. In pigs receiving 5 micrograms/kg of LPS, plasma TNF-alpha was increased 10-fold at 2 h after injection and was still elevated (P < .01) at 4 h. In these same pigs, plasma concentration of IL-6 was increased at 2 h and peaked at 4 h with levels exceeding baseline values by 200-fold (P < .01). Cortisol was elevated at 2, 4, and 8 h after injection (P < .01). The increased secretion of cytokines and cortisol in pigs injected with 5 micrograms/kg of LPS was followed by an increase in protein degradation, as evidenced by PUN values that were increased two- and threefold at 8 and 12 h after injection, respectively. However, unlike previous reports in laboratory animal species, plasma glucose, NEFA, and triglycerides were not altered by LPS. Nonetheless, as the period of feed deprivation progressed from 12 to 36 h, plasma NEFA and triglycerides increased (P < .05) and plasma glucose tended to decrease. We believe that immunological challenge induces cytokine synthesis and secretion in swine which, in turn, may induce protein catabolism.

Animals↗
PubMed1991

Immunohistochemical detection of GABA in rat striatum by intraperitoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).

To study MPTP-induced muscular rigidity, we try to detect the changes of both dopamine (DA) and GABA within rat striatums by immunohistochemical means. A high dose (30 mg/kg) of MPTP i.p. injected into rats produces behavioral abnormalities (tremor and ataxia), and higher doses (greater than 60 mg/kg) develop an acutely muscular rigidity without producing a measurable histological change. GABA is induced in the striatum of 4 MPTP (30 mg/kg) i.p. treated-rats developed tremor and ataxia. But the animals recovered to an apparently normal state and are not showed GABA-immunoreactivity. Dense GABA-immunoreactivity is observed in the striatum developed muscular rigidity, when the animals are injected with 60 mg/kg MPTP i.p.. At this time, their striatums show slight decrease of DA-immunoreactivity in medium sized-spiny neurons. The results give some insight as to how DA and GABA function within the striatum with respect to the development of neuronal abnormalities. It is also suggested by our behavioral and immunohistochemical studies that effects induced by the depletion of DA within the striatum may be mediated through the inhibition of the striato-nigral GABAergic pathway, which in turn may lead to an activation of the nigrothalamic or nigro-collicular GABAergic pathway. This study indicates that the role of striatal GABAergic transmission is important in the development of muscular rigidity. The activity within the striatum can be followed with immunohistochemical technique for GABA morphologically.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗