SEARCH · Search PubMed

Results for “rat model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed2003

Genetic analysis for diabetes in a new rat model of nonobese type 2 diabetes, Spontaneously Diabetic Torii rat.

The Spontaneously Diabetic Torii (SDT) rat has recently been established as a new rat model of nonobese type 2 diabetes. In this study, we characterized diabetic features in SDT rats, and performed quantitative trait locus (QTL) analysis for glucose intolerance using 319 male (BNxSDT)xSDT backcrosses. Male SDT rats exhibited glucose intolerance at 20 weeks, and spontaneously developed diabetes with the incidence of 100% at 38 weeks, and glucose intolerance is well associated with the development of diabetes. The QTL analysis identified three highly significant QTLs (Gisdt1, Gisdt2, and Gisdt3) for glucose intolerance on rat chromosomes 1, 2, and X, respectively. The SDT allele for these QTLs significantly exacerbated glucose intolerance. Furthermore, synergistic interactions among these QTLs were detected. These findings indicate that diabetic features in SDT rats are inherited as polygenic traits and that SDT rats would provide insights into genetics of human type 2 diabetes.

Age of Onset↗

PubMed1999

Lung injury from intratracheal and inhalation exposures to residual oil fly ash in a rat model of monocrotaline-induced pulmonary hypertension.

A rat model of monocrotaline (MCT)-induced pulmonary injury/hypertension has been recently used in particulate matter (PM) health effects studies, however, results have been equivocal. Neither the mechanism by which mortality occurs in this model nor the variation in response due to differences in PM exposure protocols (i.e., a bolus dose delivered intratracheally versus a similar cumulative dose inhaled over three days) have been fully investigated. Sprague Dawley rats (SD, 60 d old; 250-300 g) were injected with either saline (healthy) or MCT, 60 mg/kg, i.p. (to induce pulmonary injury/hypertension). Ten days later they were exposed to residual oil fly ash (ROFA), either intratracheally (IT; saline, 0.83 or 3.33 mg/kg) or by nose-only inhalation (15 mg/m3 x 6 h/d x 3 d). Lung histology, pulmonary cytokine gene expression (0 and 18 h postinhalation), and bronchoalveolar lavage fluid (BALF) markers of injury were analyzed (24 and 96 h post-IT; or 18 h post-inhalation). Data comparisons examined three primary aspects, 1) ROFA IT versus inhalation effects in healthy rats; 2) pulmonary injury caused by MCT; and 3) exacerbation of ROFA effects in MCT rats. In the first aspect, pulmonary histological lesions following ROFA inhalation in healthy rats were characterized by edema, inflammatory cell infiltration, and thickening of alveolar walls. Increases in BALF markers of lung injury and inflammation were apparent in ROFA-IT or nose-only exposed healthy rats. Increased IL-6, and MIP-2 expression were also apparent in healthy rats following ROFA inhalation. In regards to the second aspect, MCT rats exposed to saline or air showed perivascular inflammatory cell infiltrates, increased presence of large macrophages, and alveolar thickening. Consistently, BALF protein, and inflammatory markers (macrophage and neutrophil counts) were elevated indicating pulmonary injury. In regards to the third aspect, 58% of MCT rats exposed to ROFA IT died within 96 h regardless of the dose. No mortality was observed using the inhalation protocol. ROFA inhalation in MCT rats caused exacerbation of lung lesions such as increased edema, alveolar wall thickening, and inflammatory cell infiltration. This exacerbation was also evident in terms of additive or more than additive increases in BALF neutrophils, macrophages and eosinophils. IL-6 but not MIP-2 expression was more than additive in MCT rats, and persisted over 18 h following ROFA. IL-10 and cellular fibronectin expression was only increased in MCT rats exposed to ROFA. In summary, only the bolus IT ROFA caused mortality in the rat model of lung injury/hypertension. Exacerbation of histological lesions and cytokine mRNA expression were most reflective of increased ROFA susceptibility in this model.

Administration, Inhalation↗

PubMed1980

Rat model for carcinogenesis in ureterosigmoidostomy.

A rat model is used to study the carcinogenesis that occurs when urine is surgically diverted into the fecal stream, as in ureterosigmoidostomy. Adenocarcinoma of the colon occurs adjacent to the urine inlet. It is completely prevented by proximal diversion of the feces, implying that fecal carcinogens are activated locally by the urine or the urothelium.

Adenocarcinoma↗

PubMed2004

[Effect of jiangu granule on quality of bone in model rats with osteoporosis induced by ovariectomy].

OBJECTIVE: To study the effect of Jiangu granule (JGG) on quality of bone in model rats with osteoporosis. METHODS: Osteoporosis model was established by means of ovariectomy. Bone mineral density (BMD) was measured with dual energy X-ray densitometry. Osseous tissue structure of upper tibia was observed by ono-decalcified section and toluidine blue staining, and morphometry was carried out. Compressive strength limit and elastic modulus of first lumbar vertebrae, and bend load of femur were measured by light-based elastometer. RESULTS: JGG can significantly increase BMD, area of trabecula and thickness of bone cortex/diameter of marrow cavity ratio of model rats, to elevate the compressive strength limit of vertebrae and bend load of femur. CONCLUSION: JGG could increase BMD of osteoporosis model rats, and also could effectively improve the structure of osseous tissue, biomechanical property of bone and enhance the overall quality of bone.

Absorptiometry, Photon↗

PubMed2004

A modified rat model for hepatocellular carcinoma.

BACKGROUND: Rat hepatocellular carcinoma (HCC) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treatments (drug, hepatectomy and liver transplantation), and designing cancer prevention strategies. In this study we established a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general conditions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group (group A) and modified DENA-induction-HCC group(group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C developed diffusive hepatocellular carcinoma and liver cirrhosis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.

Animals↗

PubMed1996

Determination of cardiorespiratory function and the optimum anesthetic regimen during laparoscopic surgery in the rat model.

BACKGROUND: The rat is increasingly being used in laparoscopic research yet the hemodynamic and respiratory effects of CO2 pneumoperitoneum have not been studied in this model. METHODS: Five Lewis rats were anesthetized with inhaled isoflurane (1.4-2.0%) and a 50% O2/50% N2O mixture by mask (ISO). Another five rats were anesthetized with 1 ml/kg intraperitoneal sodium pentobarbital (PB) and given 100% O2 by mask. Catheters were placed in the femoral artery and the right jugular vein and a thermistor probe was placed in the aortic arch. Heart rate (HR), blood pressure (MAP), cardiac index (CI), arterial pH, and PCO2 were measured at baseline and following 10, 20, and 30 min of 2 mmHg CO2 pneumoperitoneum. RESULTS: CO2 pneumoperitoneum had no effect on HR, MAP, CI, pH, or PCO2 in either the ISO or PB anesthetic groups. Comparing the two anesthetic groups, PB demonstrated a significantly higher MAP at all time points, a significantly higher PCO2 at baseline, and 10 min of pneumoperitoneum, a significantly lower pH at baseline, 10, and 30 minutes of pneumoperitoneum, and a significantly longer induction time (31 vs. 6 min). There was no difference in HR or CI between the two anesthetics. CONCLUSION: Low-pressure CO2 pneumoperitoneum up to 30 min in the spontaneously breathing rat does not significantly affect HR, MAP, CI, pH, or PCO2. Inhalational isoflurance/N2O anesthesia produces less hypertension and respiratory acidosis than intraperitoneal pentobarbital during pneumoperitoneum in the rat.

Anesthesia, Inhalation↗

PubMed2002

Fas/Fas ligand pathway is involved in the resolution of type II pneumocyte hyperplasia after acute lung injury: evidence from a rat model.

OBJECTIVE: We used a rat model of acute lung injury to evaluate the role of apoptosis of type II pneumocytes in alveolar remodeling during the resolution phase. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Sprague-Dawley rats had Escherichia coli lipopolysaccharide instilled transtracheally to induce acute lung injury. Animals were killed on various days after lipopolysaccharide instillation. Lung specimens from all animals were examined for the presence of apoptosis in type II pneumocytes by an in situ apoptosis assay and for proliferative nuclear antigen, cytokeratin-18, Fas, and Fas ligand with an immunohistochemical stain. Fas and Fas ligand expression in both lung tissue and bronchoalveolar lavage fluid was examined by Western blot analysis. MEASUREMENTS AND MAIN RESULTS: Histologic examination revealed that the lungs of rats with acute lung injury showed infiltration of numerous inflammatory cells in the intra-alveolar and/or interstitial space and hyperplasia of type II pneumocytes. Type II pneumocyte proliferation, detected by proliferative nuclear antigen staining, developed maximally around day 3 after acute lung injury. In the in situ apoptosis assay, positive signals in type II pneumocytes were obvious and were distributed diffusely in the lung parenchyma from day 1 after acute lung injury, became maximal around day 7, then declined until day 21. DNA fragmentation analysis revealed that a DNA ladder pattern was detectable from day 3, persisted until day 10, and disappeared after day 14. The major cell types expressing Fas ligand are macrophages and neutrophils. Western blot analysis showed that Fas ligand, both membrane-bound form and soluble form, was present from day 1 to day 21 after acute lung injury, with highest level occurring during the first week of acute lung injury. Fas expression in type II pneumocytes reached its maximum on days 3-5 and then gradually declined until day 21. Fas and Fas ligand expression appeared to proceed type II pneumocyte apoptosis. After the acute stage, Fas and Fas ligand expression declined, and type II pneumocyte apoptosis also decreased. These findings correlate with histologic resolution of type II pneumocyte hyperplasia. CONCLUSIONS: Our results confirm that type II pneumocyte proliferation in response to acute lung injury is mainly a reparative phenomenon. During the resolution phase of acute lung injury, extensive apoptosis of type II pneumocytes is the main cellular mechanism that accounts for the disappearance of these cells, and Fas/Fas ligand is involved in the resolution of type II pneumocytes. Our model may provide a useful tool to assess the mechanisms of tissue remodeling after acute lung injury.

Animals↗

PubMed1999

The need to handicap the recipient's native liver in the rat model of heterotopic auxiliary liver transplantation.

In the rat model of heterotopic auxiliary liver transplantation (HALTx), the opinion varies on whether and how the recipient's native liver should be handicapped. To avoid atrophy of the transplanted organ, in this study, two different handicaps were evaluated and their effects on post-operative animal survival and liver biology are described. With a sole portacaval shunt (group 1) all rats survived longer than 3 months. An additional handicap of the liver with either a 68% partial hepatectomy (68% PH) (group 2), or both a 68% PH and a common bile duct ligation (CBDL) (group 3) led to a 100% mortality within 2 days after surgery. When an auxiliary liver was transplanted to the rats handicapped with a 68% PH (group 4), serum Bilirubin and ALAT values were significantly lower than those handicapped with both a 68% PH and a CBDL (group 5). Autopsy and histology of the long-term survivors revealed the atrophy of the engrafted livers and the regeneration of the native livers in group 4, whereas it showed the opposite in group 5. Thus the various manipulations of the native liver do influence differently the post-transplant animal survival, serum liver biochemistry and the outcome of the engrafted liver in this rat model of HALTx.

Animals↗

PubMed2004

[Effect of tianyuan ketong recipe on the pain behavior, c-fos expression and P substance contents in dorsal horn of spinal cord in formalin induced pain model rats].

OBJECTIVE: To observe the effect and mechanism of Tianyuan Ketong recipe (TKR) on the pain reaction in formalin induced pain model rats. METHODS: The analgesic effect of TKR was evaluated using pain behavior graded scoring, the c-fos gene expression and P substance contents in superficial lamella of spinal cord dorsal horn in model rats were analyzed by means of immunohistochemical analysis and computer image analysis technique. RESULTS: TKR could markedly inhibit the pain reaction in model rats (P < 0.05), and the pain induced elevation of c-fos expression and P substance contents could also be suppressed (P < 0.05). CONCLUSION: TKR shows definite analgesic effect on formalin induced pain model rats, the reduction of neuron's reaction in spinal cord dorsal horn to afferent noxious stimulation is possibly one of the pathways for its analgesic effect.

Analgesics, Non-Narcotic↗

PubMed2000

Effects of Re-arterialization on early graft function and regeneration in the rat model of heterotopic auxiliary liver transplantation.

In the rat model of heterotopic auxiliary liver transplantation, graft re-arterialization may influence the outcome of inter-liver competition. This was investigated in the current study using two transplanted groups with or without graft re-arterialization. Immediately after reperfusion, the re-arterialized grafts showed significantly higher bile flow rate and bilirubin excretion than the grafts without re-arterialization. DNA synthesis rate was also increased more drastically in the re-arterialized group following the transplantation. Without re-arterialization, the rats developed more pronounced cytolysis and cholestasis. Among the long-term survivors, all healthy re-arterialized grafts regenerated, whereas 5/6 non-re-arterialized grafts atrophied. These data demonstrate that the re-arterialization increases graft survival by improving early hepatic function, enhancing regenerative response and preventing post-transplant biliary complications in this rat model.

Animals↗

PubMed2003

Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy.

PURPOSE: To establish a rat model of neurotrophic keratopathy and to examine the effects of the combination of substance P (SP) and insulin-like growth factor (IGF)-1 on corneal epithelial barrier function and wound healing in this model. METHODS: Corneal denervation was achieved by thermocoagulation of the ophthalmic branch of the trigeminal nerve. A modified Schirmer test was performed without topical anesthesia. Corneal epithelial barrier function was assessed by measurement of fluorescein permeability with an anterior fluorophotometer. Epithelial wound healing was evaluated by measurement of the area of the defect at various times after removal of the entire epithelium. Eye drops containing both 1 mM SP and IGF-1 (1 micro g/mL) were administered six times daily. RESULTS: The Schirmer test result in eyes subjected to trigeminal denervation was lower than that in control eyes. The fluorescein permeability of the corneal epithelium of denervated eyes was increased relative to that of control eyes. Furthermore, trigeminal denervation induced a delay in corneal epithelial wound healing. Application of eye drops containing SP and IGF-1 to denervated corneas restored the fluorescein permeability of the corneal epithelium to control levels and abolished the delay in epithelial wound healing. CONCLUSIONS: A rat model of neurotrophic keratopathy, characterized by reduced tear secretion, loss of corneal sensation, impaired epithelial barrier function, and delayed epithelial wound healing, was established by trigeminal denervation. Treatment with both SP and IGF-1 improved corneal epithelial barrier function and stimulated corneal epithelial wound healing in this model.

Animals↗

PubMed2006

Catabolic effects of gastric bypass in a diet-induced obese rat model.

PURPOSE OF REVIEW: In the USA, 8-10 million people are morbidly obese, which is associated with a high frequency of comorbidities. The most effective treatment is surgery. Of around 180,000 bariatric operations performed in 2005, 80% were Roux-en-Y gastric bypass, consisting of a small gastric pouch to minimize food intake and a Roux-en-Y of distal small bowel bypassing the upper gastrointestinal tract. The precise mechanisms whereby Roux-en-Y gastric bypass achieves sustained weight loss remain unknown. To gain insight into the catabolic events of sustained weight loss we developed a diet-induced obese Roux-en-Y gastric bypass rat model. We review our rat model data from the novel viewpoint of the catabolic state, comparing it with the limited human data available and the catabolic events occurring in cancer anorexia/cachexia syndrome. RECENT FINDINGS: Current data suggest the involvement of mechanisms other than restrictive and malabsorptive factors of the Roux-en-Y gastric bypass, classically thought of as the mechanisms responsible for weight loss. Based on available data, gastrointestinal hormones and cytokines play a key role in reducing food intake and regulating energy homeostasis. Because of the cross talk between peripheral modulators and the hypothalamus, a critical role for their interaction in the outcome of Roux-en-Y gastric bypass is emerging. SUMMARY: In our Roux-en-Y gastric bypass rat model many of the changes in gastrointestinal hormones, adipokines and cytokines as well as in hypothalamic neuropeptides and neurotransmitters resemble the changes observed in the anorexia/cachexia rat model, suggesting that Roux-en-Y gastric bypass triggers a catabolic state responsible for loss of appetite and prolonged body weight reduction.

Animals↗

PubMed1998

Studies of iron deposits, inducible nitric oxide synthase and nitrotyrosine in a rat model for esophageal adenocarcinoma.

A rat model was developed recently in our laboratory to study the pathogenesis of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Eight-week-old male Sprague-Dawley rats underwent esophagoduodenal anastomosis (EDA) to produce gastric and duodenal reflux in their distal esophagi. The rats were given iron dextran (50 mg of Fe/kg, i.p.) starting 2 weeks after surgery and this was continued once a month. BE was observed as early as week 3 and the incidence of BE and EAC increased with time: 58 and 17% at week 23; 91 and 73% at week 31. There was a progression in epithelial cell proliferation and inflammation from mild to severe in the distal one-third of the esophagus. Iron deposition in the esophagus also increased with time. Iron deposits in the stromal tissue adjacent to the epithelium in the distal one-third of the esophagus were associated with areas of severe inflammation. Immunohistochemical analysis showed positive inducible nitric oxide synthase (iNOS) expression in the stromal macrophages directly beneath the epithelium in the distal one-third of the esophagus in 36, 83 and 100% of the rats at weeks 17, 23 and 31, respectively. A significant increasing linear trend (P=0.001) was seen in nitrotyrosine immunostaining (number of positive cells/high power field) in the distal esophagus. Strong positive nitrotyrosine staining was seen in the macrophages and weaker positive staining was seen in the adjacent epithelium starting at week 17. Furthermore, iron supplemented rats killed at week 31 had significantly higher (P < 0.05) levels of inflammation, cell proliferation, iNOS and nitrotyrosine as well as more tumors in their distal esophagi than did rats that received no iron supplement. These results suggest that iron supplementation enhanced inflammation and the production of reactive oxygen and nitrogen species in the esophageal epithelium. These processes could contribute to the formation of BE and its progression to EAC.

Adenocarcinoma↗

PubMed2005

Effects of electroacupuncture on the contents of NO, ET and T-AOC in the brain tissues of the cerebral hemorrhage model rats.

In the cerebral hemorrhage model rats established by injection of collagenase and heparin into caudate nucleus, the effects of electroacupuncture (EA) on the contents of nitric oxide (NO) and endothelin (ET), and total anti-oxidation capability (T-AOC) in the brain tissues were investigated. It is found that the content of NO in the Shuigou EA group lowered, ET decreased and the T-AOC raised significantly in both the Fengfu EA group and the Shuigou EA group (all P<0.05) as compared with the model group, indicating that acupuncture can reduce the contents of ET and NO, and increase the T-AOC in the brain tissues of the rats with cerebral hemorrhage.

Animals↗

PubMed2002

[Establishment and optimization of rat models for hepatic oval cells proliferation].

OBJECTIVE: To establish a rat model for hepatic oval cell proliferation and to observe the relationship between 2-acetaminofluorene (AAF) dosage and oval cell proliferation in the rat liver. METHODS: Male Wistar rats weighing 150 g received daily oral gavage of AAF for 4 days before operation and up to 7 days after operation. Two-thirds hepatectomy was performed on the 5th day and the gavage was not performed on the day of operation. AFF was given with the dosage of 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 15 mg/kg, and 20 mg/kg body weight. Animals in control group were given saline. Three rats from each group were killed every 2~3 days after hepatectomy and liver slices were fixed and processed for routine histology and immunohistochemistry. RESULTS: Hepatic oval cells were not observed in the liver of controls and only a few were detected in the liver of 2.5 mg/kg and 5 mg/kg groups. However, obvious oval cell proliferation was seen in the liver of 10 mg/kg, 15 mg/kg, and 20 mg/kg groups. Hepatic oval cells were stained positive for cytokeratin 19, OV6, vimentin and proliferating cell nuclear antigen (PCNA). CONCLUSIONS: Satisfactory rat models for hepatic oval cell proliferation can be obtained using our scheme when AAF is dosed at 10~20 mg/kg body weight.

Animals↗

PubMed1995

Antipyrine pharmacokinetics in the tail-suspended rat model.

As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greater concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our study was to examine the effects of simulated weightlessness on the pharmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total of 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day-1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated weightlessness. In addition, clearance was elevated after 1 day of tail-suspension in the p.o. dosing group. Steady-state volume of distribution was not statistically different over the entire study period in either dosing group. Data from the present study suggest that brief periods of tail-suspension may markedly alter the pharmacokinetics of drugs in the rat and that more studies are required in models of weightlessness and actual space flight to understand the complex interaction between microgravity and hepatic metabolic activity.

Administration, Oral↗

PubMed1998

Expression of Tamm-Horsfall protein in stone-forming rat models.

OBJECTIVES: To examine the expression of Tamm-Horsfall protein (THP) and calcium oxalate deposition in three rat models to clarify whether THP plays an active role in crystal formation or whether crystals induce the secretion of this protein. MATERIALS AND METHODS: A stone-forming rat model (model 1) with marked tubular dilatation in an entire kidney was produced by rendering Wistar rats (aged 8 weeks) hyperoxaluric and hypercalciuric, through compulsorily feeding with 0.12 mL of 5% ethylene glycol (in two doses daily) and 0.5 microgram of vitamin D3 every other day. Two other rat models were also produced. Model 2 comprised stone-forming rats with minimal tubular dilatation, achieved by giving rats the same dose of ethylene glycol once daily, and model 3 comprised stone-free rats with marked tubular dilatation achieved by unilateral ureteric ligation. The rats' kidneys were resected after 4 weeks and all resected kidneys immunohistochemically stained with an antibody to THP. Simultaneously, the location of calcium oxalate (CaOx) crystals was established with von Kossa staining. The relation between crystals and the secretion of THP was also assessed in vitro. Cultured renal epithelial cells (NRK-52E) were stained with an antibody to THP after they had been cultured for 72 h in a medium containing CaOx crystals. RESULTS: In model-1 kidneys with both tubular dilatation and many crystals, there was local and intense expression of THP in many renal tubules. CaOx crystals and the intense expression of THP tended to occur in the same renal tubules. In model 2 kidneys with little tubular dilatation, only a few renal tubules expressed THP strongly and the location of the crystals rarely coincided with that of THP expression. In model 3 kidneys with marked tubular dilatation but no crystals, THP was expressed strongly in many renal tubules. The expression of THP in cultured NRK-52E cells was not stimulated by CaOx crystals. CONCLUSIONS: The results from the in vivo models suggest that THP did not initiate crystal formation and the strong expression of THP was induced not by crystals but by renal tubular damage caused by tubular dilatation. From the close association of THP and crystals in model 1 kidneys, this protein might play a secondary role as an adhesive, promoting stone formation.

Adjuvants, Immunologic↗

PubMed1992

Increased ketogenesis related to insulin deficiency in isolated hepatocytes from NIDDM model rats.

To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone body production rates in hepatocytes from newly developed non-obese NIDDM model rats. NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2 or 5 days of age (STZ2, STZ5 respectively). After 10-15 weeks, ketone body production rates in hepatocytes isolated from these rats were compared with those from control rats as well as ketotic rats made by intravenous injection of streptozotocin into adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7 +/- 0.98, 14.9 +/- 0.72, 16.0 +/- 0.45, 22.8 +/- 2.32 nmole.palmitate/mg.prot/hr, respectively. These rates were stimulated by 1 microgram/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1 +/- 0.99, 18.6 +/- 1.36, 18.7 +/- 0.69 nmole.palmitate/mg.prot/hr, respectively), but not in ketotic rats (22.8 +/- 2.07 nmole.palmitate/mg.prot/hr). The similar effects were observed by 1 microgram/ml of epinephrine. The basal ketone body production rates were negatively correlated to both hepatic glycogen contents and plasma IRI levels. Considering these parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was between that in control and ketotic rats. These results indicate that the derangements of hepatic ketone body production are related to the severity of insulin deficiency and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated plasma ketone body levels in non-obese NIDDM.

Animals↗