Injection Of Gold Thioglucose Research Articles

Effects of Gold Thioglucose Treatment on Central Corticotrophin‐Releasing Hormone Systems in Mice

Systemic administration of gold thioglucose (GTG) causes a hypothalamic lesion that extends from the ventral part of the ventromedial hypothalamus (VMH) to the dorsal part of the arcuate nucleus (ARC), resulting in hyperphagia and obesity in mice. In the present study, we used in situ hybridisation histochemistry to explore the effects of GTG on the central corticotrophin-releasing hormone (CRH) system, which regulates feeding and energy homeostasis. Type 2 CRH receptor (CRHR-2) mRNA expression decreased by 40% at 8 weeks in the VMH and by 40-60% at 2 and 8 weeks in the ARC after GTG injection. By contrast, CRHR-2 mRNA expression in the hypothalamic paraventricular nucleus (PVN) and lateral septum was unchanged. Urocortin (Ucn) 3 mRNA expression in the perifornical area and medial amygdala decreased, whereas CRH mRNA expression in the PVN increased at 2 and 8 weeks after GTG injection. Ucn 1 mRNA expression in the Edingher-Westphal nucleus and Ucn 2 mRNA expression in the PVN were unchanged. Because Ucn 3 is an anorexigenic and a possible endogenous ligand for VMH CRHR-2, our results suggest that decreased Ucn 3 expression and decreased VMH CRHR-2 expression contribute, in part, to GTG-induced hyperphagia and obesity. To determine whether VMH CRHR-2 mediates the anorexigenic effects of Ucn 3, Ucn 3 was administered i.c.v. and food intake was measured 8 weeks after GTG treatment. Ucn 3 decreased cumulative food intake on days 4-7 after surgery compared to i.c.v. administration of vehicle in control mice. By contrast, the anorexigenic effects of i.c.v. Ucn 3 were abolished in GTG-treated mice. Taken together, our results indicate that the Ucn 3 pathway, which innervates the VMH, is involved in appetite regulation via CRHR-2. It remains to be determined whether CRHR-2 in the ARC has additional roles in appetite regulation by Ucn 3.

Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

To clarify effects of diet and body weight on prostate cancer development, three studies were undertaken using the TRAMP mouse model of this disease. In the first experiment, obesity was induced by injection of gold thioglucose (GTG). Age of prostate tumor detection (~33 wk) and death (~43 wk) was not significantly different among the groups. In the second study, TRAMP-C2 cells were injected into syngeneic C57BL6 mice and tumor progression was evaluated in mice fed either high-fat or low-fat diets. The high fat fed mice had larger tumors than did the low-fat fed mice. In the third study, tumor development was followed in TRAMP mice fed a high fat diet from 6 weeks of age. There were no significant effects of body weight status or diet on tumor development among the groups. When the tumors were examined for the neuroendocrine marker synaptophysin, there was no correlation with either body weight or diet. However, there was a significant correlation of the expression of synaptophysin with earlier age to tumor detection and death. In summary, TRAMP-C2 cells grew faster when the mice were fed a high-fat diet. Further synaptophysin may be a marker of poor prognosis independent of weight and diet.

Reversal of acute streptozotocin-induced glycemic changes by chemical ventro-medial hypothalamic lesions.

This report describes the effect of chemical gold thioglucose (GTG) lesions of the ventromedial hypothalamic (VMH) nuclei in male Sprague-Dawley rats previously made diabetic by injection of streptozotocin (50 mg/kg, i.v.). Injection of streptozotocin resulted in hyperglycemia (blood glucose greater than 200 mg%) within one week; treatment of these rats with intracerebroventricular (ICV) injections of GTG (0.025 M) + Insulin (1 microU) reversed these glycemic changes within six weeks. On the basis of these initial experiments, it has been shown that GTG lesions of the VMH may reverse glycemic changes in acute streptozotocin-induced diabetes.

BRAIN LESIONS AND HYPOTHALAMIC GOLD DEPOSITION FOLLOWING GOLDTHIOGLUCOSE INJECTION.

Journal Article Brain Lesions and Hypothalamic Gold Deposition following Goldthioglucose Injection Get access Nutrition Reviews, Volume 23, Issue 8, August 1965, Pages 252–255, https://doi.org/10.1111/j.1753-4887.1965.tb02165.x Published: 01 August 1965

Fos activation in the lower brainstem after feeding and refeeding in gold thioglucose-treated mice

Event Abstract Back to Event Fos activation in the lower brainstem after feeding and refeeding in gold thioglucose-treated mice Péter Kurucz1*, Kinga Ibolya1, Meltzer K. Szabó1 and Miklos Palkovits1 1 Hungarian Academy of Sciences and Semmelweis University, Hungary Single injection of gold thioglucose (GTG) lesions the hypothalamic ventromedial nucleus in mice and increases food intake and obesity. It is also known that GTG treatment produces lesions in the lower brainstem as well: in the nucleus of the solitary tract (NTS), the dorsal motor nucleus of vagus (DMV) and the area postrema (AP). In the present study, acute responses to fasting and refeeding were investigated by immunohistochemical detection of Fos expression in neurons located in these brain areas of GTG lesioned and control mice. Very strong Fos activity was seen in the DMV and AP in control mice after 2 days fasting, while the NTS was silent. GTG-treated, fasted animals showed similar pattern of Fos distribution but with reduced number of immunoreactive neurons in all three investigated nuclei. In control mice, refeeding increased Fos activity in the NTS and AP while the DMV remained silent. In GTG-treated mice, feeding produced Fos immunoreactivity in the same areas but the intensity was lower than that in saline-injected control mice. In summary, refeeding elicited activity in the nucleus of the solitary tract and the area postrema neurons was reduced by GTG. In GTG-treated animals fasting produced lower intensity changes in the activity of the preganglionic dorsal motor vagal neurons but not in the viscerosensory NTS. These results are similar to our previous findings concerning on the effect of fasting and refeeding in the vagal nuclei of monosodium glutamate treated rats. Supported by OTKA K 62893. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Homeostatic regulatory mechanisms Citation: Kurucz P, Ibolya K, Szabó MK and Palkovits M (2009). Fos activation in the lower brainstem after feeding and refeeding in gold thioglucose-treated mice. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.114 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Mar 2009; Published Online: 04 Mar 2009. * Correspondence: Péter Kurucz, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary, kuruczp@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Péter Kurucz Kinga Ibolya Meltzer K Szabó Miklos Palkovits Google Péter Kurucz Kinga Ibolya Meltzer K Szabó Miklos Palkovits Google Scholar Péter Kurucz Kinga Ibolya Meltzer K Szabó Miklos Palkovits PubMed Péter Kurucz Kinga Ibolya Meltzer K Szabó Miklos Palkovits Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Differential response of arcuate proopiomelanocortin- and neuropeptide Y-containing neurons to the lesion produced by gold thioglucose administration

The effect of gold thioglucose (GTG) administration on neurons containing feeding-related peptides in the hypothalamic arcuate nucleus was examined in mice. Intraperitoneal GTG injection increased the body weight and produced a hypothalamic lesion that extended from the ventral part of the ventromedial nucleus to the dorsal part of the arcuate nucleus. Neurons containing proopiomelanocortin (POMC) and neuropeptide Y (NPY) present in the dorsal part of the arcuate nucleus were destroyed by GTG. In addition, the peptide-containing fibers that extended from the remaining arcuate neurons were degenerated at the lesion site. The number of POMC-containing fibers in the paraventricular nucleus, dorsomedial nucleus, and lateral hypothalamus was found to have decreased significantly when examined at 2 days and 2 weeks after the GTG treatment. In contrast, the number of NPY-containing fibers in the lateral hypothalamus remained unchanged after the GTG treatment, probably because of the presence of an unaffected NPY-containing fiber pathway passing through the tuberal region and projecting onto the lateral hypothalamus. The number of NPY-immunoreactive fibers in the paraventricular and dorsomedial nuclei showed a moderate but significant decrease at 2 days after the GTG treatment, but it recovered to the normal levels 2 weeks later. The NPY-containing fibers were found to have regenerated across the lesion site 2 weeks later, and this might contribute to the recovery of the NPY-immunoreactive fibers in these regions. The present results first demonstrate that POMC- and NPY-containing neurons in the arcuate nucleus respond differently to the lesion produced by the GTG treatment.

D- chiro-Inositol enhances effects of hypothalamic toxin gold-thioglucose

d- chiro-Inositol (DCI) enhances reproductive function in insulin-resistant women with polycystic ovarian disease and enhances the effects of insulin in the periphery, suggesting that this compound may act in part by sensitizing the hypothalamus to effects of insulin. Effects of gold-thioglucose (GTG) to produce hypothalamic lesions and subsequent obesity are insulin-dependent, suggesting that responses to GTG may be a marker of hypothalamic sensitivity to insulin. To assess these hypotheses, the present study assessed if DCI would enhance the ability of a subthreshhold dose of GTG to produce hypothalamic lesions and subsequent obesity. At the subthreshhold dose used (0.4 mg/kg i.p.), injection of GTG produced no subsequent effect on body weight compared to saline; similarly, at the dose of DCI used (10 mg/kg/day in drinking water), DCI produced no effect on body weight. In contrast, when given to mice exposed to DCI, this dose of GTG produced significant increase in body weight and evidence of an enhanced medial arcuate hypothalamic lesion.

Production and characterization of Reg knockout mice: reduced proliferation of pancreatic beta-cells in Reg knockout mice.

Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets. We have demonstrated in vitro and in vivo that the exogenous addition of rat and human Reg gene products, Reg/REG proteins, induced beta-cell replication via the Reg receptor and thereby ameliorated experimental diabetes. In the present study, we produced Reg knockout mice by homologous recombination. The Reg gene disruption resulted in a null mutation. Knockout mice developed normally. Islets from the Reg knockout mice appeared morphologically indistinguishable from those of normal controls. However, [(3)H]thymidine incorporation in isolated islets from Reg knockout mice was decreased. When hyperplastic islets were induced by the injection of goldthioglucose, the average islet size in Reg knockout mice was significantly smaller than that of control Reg(+/+) mice. We then produced transgenic mice carrying the Reg gene under the control of the rat insulin II promoter (Ins-Reg) to express Reg in beta-cells. Isolated islets from the Ins-Reg transgenic mice showed increased [(3)H]thymidine incorporation. By intercrossing, we produced NOD mice carrying the Ins-Reg transgene and found that development of diabetes in the resultant Ins-Reg transgenic NOD mice was significantly retarded, coinciding with an increase in the pancreatic beta-cell mass. These results indicate that Reg plays an important role in beta-cell growth/regeneration.

Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis.

Leptin-deficient ob/ob mice are protected from Con A-induced hepatitis. However, it is unclear whether leptin deficiency or obesity itself is responsible for this protection. To address this question, wild-type (WT) obese mice with high serum leptin levels were generated by injection of gold thioglucose (WT GTG). Both Con A-injected WT and WT GTG mice developed hepatitis, whereas no hepatic damage was observed in ob/ob mice. Moreover, TNF-alpha and IFN-gamma levels as well as expression of the activation marker CD69 were elevated in liver mononuclear cells of WT and WT GTG mice, but not in ob/ob mice following administration of Con A. The liver of WT and WT GTG mice had the same percentage of NK T cells, a lymphocyte population involved in Con A-induced hepatitis. This population decreased equally in both WT and WT GTG mice after Con A injection. In contrast, the liver of ob/ob mice contained 50% less NK T cells compared to WT and WT GTG mice. Furthermore, no decrease in NK T cells was observed in Con A-injected ob/ob mice. We conclude that leptin-deficiency, not obesity, is responsible for protection from Con A-induced hepatitis.

Decreased Resistin Expression in Mice with Different Sensitivities to a High-Fat Diet

The regulation of resistin, a new adipose-derived circulating factor, is the subject of controversy. In particular, the question of its modulation in obesity led to opposite results reported by two different groups. In the current study, we assayed adipocyte resistin mRNA using fluorescent real-time RT-PCR. We studied the expression of resistin in mice which are differently sensitive to diet-induced obesity: the FVB/n strain, which poorly responds to high-fat diet and transgenic mice that express human α2A-AR in adipose tissue in the absence of β3-adrenergic receptor (AR) under the FVB genetic background which are highly sensitive to high-fat diet and develop hyperplastic obesity. We observed that FVB mice, which have no significant increased body weight after an 8-week high-fat diet period, exhibited no alteration of resistin expression. In contrast, the transgenic mice developing high-fat diet-induced obesity exhibited markedly downregulated adipocyte resistin mRNA. We also showed that obesity induced by gold thioglucose injection in FVB/n mice reduces the expression of resistin in isolated adipocytes. This argues for decreased expression of resistin as a hallmark of obesity. Moreover, our data show that feeding a high-fat diet is not a primary determinant of resistin regulation.

Increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals.

We have recently demonstrated that insulin activates farnesyltransferase (FTase) and thereby increases the amounts of cellular farnesylated p21Ras in 3T3-L1 fibroblasts, adipocytes and vascular smooth muscle cells. We postulated that hyperinsulinaemia might considerably increase the the cellular pool of farnesylated p21Ras available for activation by other growth factors. To examine the role of in vivo hyperinsulinaemia in regulating farnesylated p21Ras, we measured the amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals. Liver, aorta, and skeletal muscle of ob/ob mice, and mice made obese and hyperinsulinaemic by injection of gold-thioglucose contained greater amounts of farnesylated p21Ras than tissues of their lean normoinsulinaemic counterparts. Similarly, farnesylated p21Ras was increased (67 vs. 35 % in control animals, p<0.01) in the livers of hyperinsulinaemic Zucker rats (fa/fa). Reduction of hyperinsulinaemia by exercise training (2 h/day for 7-8 weeks) resulted in decreases in the amounts of farnesylated p21Ras in these animals. Increased farnesylated p21Ras in hyperinsulinaemic animals reflected increasing increments in the activity of FTase in ob/ob mice (2-fold increase) and fa/fa Zucker rats (3.5-fold increase), while the total amounts of Ras proteins remained unchanged. In contrast to insulin-resistant hyperinsulinaemic animals, denervated insulin-resistant rat soleus muscle (in the presence of normoinsulinaemia) showed normal amounts of farnesylated p21Ras. In summary, these data confirm increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals.

Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin.

Genetic obesity is associated with increased neuropeptide Y (NPY) messenger RNA (mRNA) and decreased POMC mRNA in the hypothalamus of ob/ob and db/db mice, or impaired sensitivity to alphaMSH (derived from POMC) in the yellow agouti mouse. Acquired obesity can be produced by chemically lesioning the hypothalamus with either monosodium glutamate (MSG) in neonates or gold thioglucose (GTG) in adult mice. The present study examined whether elevated NPY mRNA and/or decreased POMC mRNA in the hypothalamus are associated with obesity due to hypothalamic lesions. GTG injection into adult mice produced a profound obese phenotype, including hyperphagia, increased body weight, and increased leptin mRNA and peptide, in association with reduced hypothalamic NPY mRNA and POMC mRNA. MSG treatment produced virtual elimination of NPY mRNA in the arcuate nucleus and a reduction of hypothalamic POMC mRNA, and led to elevated leptin. MSG pretreatment did not attenuate GTG-induced hyperphagia and obese phenotype. These results do not support a role for NPY-synthesizing neurons in the arcuate nucleus in mediating hypothalamic acquired obesity, but are consistent with the hypothesis that decreased activity of hypothalamic neurons synthesizing POMC play a role in mediating hypothalamic obesity.

Exploring the expression of the melanin-concentrating hormone messenger RNA in the rat lateral hypothalamus after goldthioglucose injection

Melanin-concentrating hormone (MCH) is expressed in a large neuronal population of the rat lateral hypothalamus. This area is known to be implicated in the regulation of thirst and hunger and to contain glucose-sensitive cells. In the present study, we investigated the effects of goldthioglucose (GTG), a toxic form of glucose, on the expression of the MCH gene in the rat lateral hypothalamus by immunocytochemistry, in situ hybridization and competitive RT-PCR. We observed that the MCH immunoreactivity and the level of MCH mRNA were not changed after intraperitoneal GTG injection (0.35 mg/g body weight). These results together with previous data suggest that the glucose-sensitive cells of the lateral hypothalamus are different from the MCH neurons and remain to be identified.

Injection with gold thioglucose impairs sensitivity to glucose: evidence that glucose-responsive neurons are important for long-term regulation of body weight

It has been proposed, but never demonstrated, that glucose-responsive neurons are essential for the long-term regulation of body weight, and that mice injected with gold-thio-glucose (GTG) become obese due to destruction of glucose-responsive neurons. To assess these hypotheses, mice were injected with either saline (control) or a dose of GTG that produces obesity, and the effects on feeding of peripheral injection of saline, glucose, 2-deoxyglucose (2-DG), or cholecystokinin (CCK) were measured. In control mice, 2-DG increased, whereas glucose and CCK decreased, food intake significantly. In contrast, in GTG-treated mice, 2-DG and glucose did not have a significant effect on food intake. The GTG-treated mice remained sensitive to the inhibitory effect of CCK on food intake. These data indicate that i.p. injection of GTG, which produces obesity, also destroys glucose-responsive neurons, consistent with the hypothesis that glucose-responsive neurons contribute to the long-term regulation of body weight.

Injection with gold thioglucose impairs sensitivity to glucose: evidence that glucose-responsive neurons are important for long-term regulation of body weight

It has been proposed, but never demonstrated, that glucose-responsive neurons are essential for the long-term regulation of body weight, and that mice injected with gold-thio-glucose (GTG) become obese due to destruction of glucose-responsive neurons. To assess these hypotheses, mice were injected with either saline (control) or a dose of GTG that produces obesity, and the effects on feeding of peripheral injection of saline, glucose, 2-deoxyglucose (2-DG), or cholecystokinin (CCK) were measured. In control mice, 2-DG increased, whereas glucose and CCK decreased, food intake significantly. In contrast, in GTG-treated mice, 2-DG and glucose did not have a significant effect on food intake. The GTG-treated mice remained sensitive to the inhibitory effect of CCK on food intake. These data indicate that i.p. injection of GTG, which produces obesity, also destroys glucose-responsive neurons, consistent with the hypothesis that glucose-responsive neurons contribute to the long-term regulation of body weight.

Effect of adrenalectomy on glucose tolerance and lipid metabolism in gold-thioglucose obese mice

The effect of adrenalectomy (ADX) on body weight, lipogenesis, and glucose tolerance was investigated in mice made obese by a single intraperitoneal injection of gold-thioglucose (GTG). Five weeks after ADX the weight of GTG-obese mice was significantly decreased (GTG-obese+sham-ADX: 39.8 +/- 0.8 g; GTG-obese+ADX: 27.6 +/- 1.1 g; P < 0.05). ADX also reduced serum glucose (GTG-obese+sham-ADX: 16.5 +/- 0.6 mmol/l; GTG-obese+ADX: 10.8 +/- 0.5 mmol/l; P < 0.05) and serum insulin concentrations (GTG-obese+sham-ADX: 197 +/- 36 microU/ml; GTG-obese+ADX: 38 +/- 7 microU/ml; P < 0.05) of fed GTG-obese mice and greatly improved glucose tolerance. ADX lowered liver glycogen content and reduced the fatty acid content of liver, epididymal white adipose tissue (WAT), and interscapular brown adipose tissue (BAT) of fed GTG-obese mice. Lipid synthesis in liver and WAT of GTG-obese mice was decreased by ADX, but lipogenesis in BAT was increased, possibly to provide substrate for increased thermogenesis in this tissue. Effects of ADX on metabolism were not confined to GTG-injected mice, as ADX also reduced body weight and altered the glucose tolerance of age-matched control mice. ADX increased lipid synthesis in liver, WAT, and BAT of fed control mice without an increase in lipid deposition, indicating that there was increased lipid turnover in these lipogenic tissues of ADX mice. ADX reduced the fasting blood glucose concentration of both control and GTG-obese mice to a level below that of sham-ADX control mice (sham-ADX control: 6.0 +/- 0.4 mM; ADX control: 2.9 +/- 0.5 mM; ADX GTG-obese: 3.3 +/- 0.2 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin response to an intravenous glucose load during development of obesity in gold thioglucose-injected mice.

The insulin secretory response to an intravenous glucose load was examined in chronically catheterized, conscious mice 2, 5, and 10 wk after induction of obesity by a single injection of gold thioglucose. At 2 wk after administration of gold thioglucose, a significant increase in both the insulinemia and incremental area under the curve of insulin release after intravenous glucose were observed (incremental area under the curve for 2-wk control mice, 852 +/- 54 min/pM; incremental area under the curve for 2-wk GTG-injected mice, 1140 +/- 114 min/pM; P < 0.05). At this stage, no significant difference existed in the glucose tolerance or body weight of control and gold thioglucose-injected mice. By 5 wk, the gold thioglucose-injected mice were approximately 33% heavier than their lean controls and showed a marked glucose intolerance. This was accompanied by overt hyperinsulinemia in both the basal state and also in response to an intravenous glucose bolus as indicated by the increase in the incremental area under the curve of insulin (5-wk control mice, 816 +/- 114 min/pM; 5-wk gold thioglucose-injected mice, 1374 +/- 156 min/pM; P < 0.05). At 10 wk after gold thioglucose administration, body weight and the degree of glucose intolerance were increased. Although 10-wk gold thioglucose-injected mice showed basal hyperinsulinemia, an intravenous glucose bolus elicited a smaller insulin secretory response than that observed in the age-matched lean control animals (10-wk control mice, 672 +/- 54 min/pM; 10-wk gold-thioglucose-injected mice 186 +/- 42 min/pM; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the lipogenic response to feeding of liver, white adipose tissue and brown adipose tissue during the development of obesity in the gold-thioglucose-injected mouse

Lipogenic response to feeding was measured in vivo in liver, epididymal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), during the development of obesity in gold-thioglucose (GTG)-injected mice. The fatty acid synthesis after a meal was higher in all tissues of GTG-treated mice on a total-tissue basis, but the magnitude of this increase varied, depending on the tissue and the time after the initiation of obesity. Lipogenesis in BAT from GTG mice was double that of control mice for the first 2 weeks, but subsequently decreased to near control values. In WAT, lipogenesis after feeding was highest 2-4 weeks after GTG injection, and in liver, lipid synthesis in fed obese mice was greatest at 7-12 weeks after the induction of obesity. The post-prandial insulin concentration was increased after 2 weeks of obesity, and serum glucose concentration was higher in fed obese mice after 4 weeks. These results indicate that increased lipogenesis in GTG-injected mice may be due to an increase in insulin concentration after feeding and that insulin resistance (assessed by lipogenic response to insulin release) is apparent in BAT before WAT and liver.

KK Mice—Usefulness for Evaluation of Anti-diabetic Drugs

The KK line of mice, established by Kondo et al. in 1957, is spontaneously obese, hyperinsulinemic, and often hyperglycemic; these mice are used as a model for non-insulin dependent diabetes mellitus. Although KK mice vary considerably in body weight, and blood and urinary glucose levels, they are resistant to the hypoglycemic action of insulin and intolerant to glucose. However, KK mice are predisposed to diabetes in response to the onset of obesity, induced by injection of goldthioglucose, feeding of high energy diets, or introduction of the yellow obese gene (Ay) . This predisposition is considered to be genetically determined resistant to insulin, as evidenced by impaired sensitivity of adipocytes and muscle to insulin. Obese KK mice are characterized by renal glomerular lesions consisting of a diffuse or exudative type of sclerosis, accompanied by albuminuria. These changes, though less remarkable, are observed also in non-obese KK mice. These findings indicate that KK mice are useful to evaluate new anti-diabetic and anti-obesity agents designed to improve insulin resistance and obesity-related metabolic disturbances. In the present symposium, I would like to present characteristics of KK mice, and their responses to ADD-3878, an agent to improve insulin resistance and AO-128, an intestinal disaccharidase inhibitor.

The effect of intraperitoneally administered gold thioglucose on growth, food consumption and accumulation of gold in various organs of the chicken ( Gallus domesticus)

1. 1. Gold thioglucose (GTG) was intraperitoneally injected into 10-day-old male and female chickens in a dose of 0, 0.2, 0.4 or 0.8 mg per gram of body wt. 2. 2. Mortality of the GTG-injected chickens was 100% and 25% for doses of 0.8 and 0.4 mg gBW respectively, in both sexes and 25% for a dose of 0.2 mg in females, which were all found within 14.5 hr after the GTG treatment. 3. 3. Body weight gain, food consumption and food efficiency of surviving chickens for 23 days after the GTG injection were not affected by GTG in spite of dose level. 4. 4. Gold detected in blood, heart, liver, gallbladder, spleen, proventriculus, gizzard, duodenum, kidney, pectoral muscle, small intestine, lung and brain of the dead chickens accumulated most highly in heart and followed by spleen, but in the surviving chicken a little gold was only found in liver, spleen and kidney of some GTG-treated chickens.