Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders

Background

Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.

Effects of sc administration of recombinant human insulin-like growth factor I (IGF-I) on normal human subjects

Recombinant human insulin-like growth factor I (IGF-I) was administered subcutaneously to each of 5 normal human subjects at doses of 0 mg/kg (control), 0.06 mg/kg, or 0.12 mg/kg successively at one week intervals. After 0.06 mg/kg or 0.12 mg/kg IGF-I injections, plasma IGF-I levels increased from 185 +/- 17 ng/ml (mean +/- SEM) to maximal levels of 396 +/- 21 ng/ml at 3 hours and from 169 +/- 14 ng/ml to 480 +/- 27 ng/ml at 4 hours, respectively. These two peak values were statistically different (p less than 0.05). After 0.06 mg/kg and 0.12 mg/kg IGF-I administration, blood glucose levels decreased from 85 +/- 2 mg/dl to minimal levels of 73 +/- 3 mg/dl at 3 hours and from 83 +/- 1 mg/dl to 50 +/- 4 mg/dl at 2 hours, respectively. These two minimal values were statistically different (p less than 0.001). Serum insulin and C-peptide levels were decreased in a dose dependent manner after IGF-I administration. There were no changes between blood urea nitrogen levels before and 4 hours after IGF-I administration. The urinary GH concentration decreased after 0.06 mg/kg IGF-I administration, but increased and maintained normal values after 0.12 mg/kg IGF-I administration.     

Destructive thyrotoxicosis in a patient with anaplastic thyroid cancer

A 55-year-old man was admitted to our hospital with an anterior neck tumor, hoarseness, and dysphagia that had continued for a few weeks. He was diagnosed as anaplastic thyroid cancer by fine-needle aspiration cytology. He was treated by external radiation and chemotherapy, but left hemothorax developed and he died of respiratory failure on the 76th day in hospital. On admission, the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), and TSH were 12.8 pg/ml, 4.2 ng/dl, and 0 microU/ml, respectively. The simultaneous thyroidal I-131 uptake rate was 1.2% at 24 hours. The levels of free thyroid hormones fell gradually without antithyroid drugs to result in hypothyroidism (FT3 0.8 pg/ml, FT4 0 ng/dl, and TSH 36 microU/ml). The rapid growth of anaplastic thyroid cancer seemed to be responsible for destructive thyrotoxicosis followed by hypothyroidism in this patient.     

ONTOGENETIC AND SEASONAL VARIATION IN BLOOD PARAMETERS IN SOUTHERN ELEPHANT SEALS

Blood samples were collected from 156 free-ranging southern elephant seals ( Mirounga leonina ) from Peninsula Valdes to study the variation in blood parameters related to ontogeny and the annual cycle. Samples ranged from newborn pups to adults. Interactions between age and sex showed different trends in ontogenetic changes of blood parameters (MANOVA, Wilkis' Lamb-da_12,243= 0.75, P < 0.01). The hematocrit (HCT) and hemoglobin concentration (HB) reached adult levels early in life. Weanlings had 14 % higher HCT than pups, and similar levels to juveniles and adults (HCT range = 46%-62 %). HB of males were below those of females from weaning (18.4 vs . 20.3 g/dl) to adulthood (19.8 vs . 22.3 g/dl). Red blood cell counts (RBC) did not change significantly from pups to juveniles (2.8–3.2 10⁶/μl), but varied for adults at different times of the annual cycle. Breeding females had higher RBC than molting females (3.1 vs. 2.4 10⁶/μl). Changes in blood parameters are related to the development of diving capabilities from pups to juveniles. Changes in adults were associated with different stages of the annual cycle, and these may be the result of the requirements imposed by pregnancy and fasting duration.     

Regulation of gonadotrophin secretion in rams from birth to sexual maturity. I. Plasma LH, FSH and testosterone levels.

Plasma LH, FSH and testosterone concentrations were measured by radioimmunoassays in male crossbred Merino/Corriedale sheep from birth to 45 weeks of age. FSH levels were 11 and 22 ng/ml at birth, increased to peak levels (mean value of 47 ng/ml) at 5 weeks and fluctuated between 25 and 35 ng/ml for the next 40 weeks. Similarly, LH (less than 0-5 ng/ml) and testosterone (less than 38 ng/100 ml) levels were low at birth and were significantly elevated by 5 weeks of age. LH values varied betwen 0-9 and 3-0 ng/ml for the next 30 weeks and then a secondary rise occurred reaching levels of 2-4 ng/ml by the 41st week after birth. Concentrations of LH subsequently fell to levels observed in adult rams. Testosterone levels rose gradually between the 5th and the 25th week, and then increased rapidly to values of 270-517 ng/100 ml by the 41st week after birth, a time coincident with the peak LH levels. Histological examination of testicular biopsies demonstrated that Sertoli cell maturation occurred 17-21 weeks after birth and was followed by activation of spermatogenesis leading to the presence of spermatozoa in the seminiferous epithelium by 39-42 weeks of age.     

Transient thyrotoxicosis after unilateral adrenalectomy in two patients with Cushing's syndrome

We found transient hyperthyroidism in the course of hydrocortisone withdrawal in two patients who had undergone unilateral adrenalectomy to resect cortisol-hypersecreting adenoma. A 38-yr-old woman showed clinical thyrotoxicosis 3 months after the operation. Serum T4, T3 and TBG levels were 11.9 micrograms/dl, 310 ng/dl and 16.5 micrograms/ml, respectively. She was given methimazole (MMI) 15 mg/day for 4 weeks. After the cessation of MMI treatment, she eventually recovered to the euthyroid state. The other patient, a 34-yr-old man showed very mild clinical symptoms of hyperthyroidism 2 months after the operation. Serum T4, T3 and TBG levels were 10.4 micrograms/dl, 240 ng/dl and 14.5 micrograms/ml, respectively. In this case, no antithyroid drug was given. Two to three months after the onset of hyperthyroidism, he returned to the euthyroid state spontaneously. We carefully eliminated the possibility of factitious thyrotoxicosis in both cases. They had neither neck pain nor fever. Both had low radioactive iodine uptake by the thyroid. Therefore, we diagnosed them as painless thyroiditis induced after the resection of hypersecreting adrenal adenoma.     

Metoclopramide,a dopamine antagonist,stimulates aldosterone secretion in rhesus monkeys but not in dogs or rabbits

This study was designed to investigate the role of dopamine in the control of aldosterone secretion in three frequently used laboratory animals. Five New Zealand rabbits, five mongrel dogs and five rhesus monkeys received metoclopramide (MCP) (200 μg/kg iv) and blood samples were collected at 0,5,15,30 and 45 minutes after drug administration. MCP had no effect on plasma aldosterone concentrations at any sampling time in the rabbits or dogs. However, MCP produced a rapid and marked increase in plasma aldosterone from 6.5±0.6 ng/dl to 18.1±2.8 ng/dl at 5 min. and a maximum level of 40.5±4.4 ng/dl at 10 min. after drug administration in the monkeys. MCP had no significant effect on plasma cortisol or plasma renin activity levels in the three species. Prolactin rose in the monkeys from 8.6±1.2 ng/ml to a maximum of 123.5±8.5 ng/ml at 15 min. after MCP. Administration of MCP resulted in a rise in plasma 18-hydroxycorticosterone in the monkeys from 12.5±1.4 ng/dl to a maximum concentration of 50.0±5.1 ng/dl 15 min. after drug administration. Plasma corticosterone, 11-deoxycorticosterone, and 18-hydroxydeoxycorticosterone were not altered by MCP. Although unlikely, it is possible that ketamine may have accounted for some of the changes in plasma aldosterone and 18-hydroxycorticosterone observed after metoclopramide in the monkeys. The findings suggest that dopamine modulates aldosterone biosynthesis in the monkey probably by regulating glomerulosa 18-hydroxylase activity.     

Characterization of hyperinsulinemic recombinant inbred (RI) strains (SMXA-5 and SMXA-9) derived from normoinsulinemic SM/J and A/J mice.

We discovered two mouse strains (SMXA-5 and SMXA-9) with hyperinsulinemia among the substrains and progenitor strains (SM/J and A/J) of the SMXA recombinant inbred (RI) strains, and characterized the two strains at 20 weeks of age. SMXA-5 (mean +/- S.E.M: 9.6 +/- 1.7 ng/ml) and SMXA-9 (7.7 +/- 1.3 ng/ml) males had higher serum immunoreactive insulin levels than SM/J (1.4 +/- 0.3 ng/ml) and A/J (1.1 +/- 0.1 ng/ml) males in the nonfasting condition. The hypoglycemic response to insulin at 30 min after injection was significantly less in SMXA-5 males than in SM/J mice. Glucose tolerance test revealed that the incidence of impaired glucose tolerant males was 58% (11/19) in SMXA-5 and 42% (10/24) in SMXA-9 strains, but none in SM/J and A/J strains. SMXA-5 (209 +/- 29 mg/dl) and SMXA-9 (235 +/- 31 mg/dl) had higher serum triglyceride levels than SM/J (126 +/- 14 mg/dl) and A/J (89 +/- 5 mg/dl) males in the nonfasting condition. Histologic examination revealed enlarged islets in the pancreas of hyperinsulinemic SMXA-5 male mice. Moreover, SMXA-5 and SMXA-9 mice exhibited mild obesity. SMXA-5 and SMXA-9 males were therefore characterized by hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia and mild obesity which resembled some of the phenotypes of human Syndrome X, although both progenitor strains were normal so far as we examined. Since the RI strains are a powerful tool to facilitate polygenic-trait analysis, SMXA-5 and SMXA-9 mice will be useful materials to investigate the genetic basis of complex diseases, and are possible new metabolic models in relation to hyperinsulinemia.     

Effect of a high protein diet on glucose tolerance in the rat model

The purpose of this study was to determine the effects of a high protein diet on glucose tolerance. Nine Sprague Dawley rats received a high protein (HP) diet (65% protein, 35% fat) and eight rats consumed a standard chow (SC) diet over eight weeks. Oral glucose tolerance tests (OGTT) were performed at the end of the third and the seventh week. The diet did not effect glucose tolerance in the first (SC=10357+/-294 mg/dl/120 min; HP=9846+/-300 mg/dl/120 min) or the second OGTT (SC=10134+/-395 mg/dl/120 min; HP=10721+/-438 mg/dl/120 min) as reflected by the area under the glucose concentration curve. Similarly, the area under the insulin concentration curve was not effected by the high protein diet during the first (SC=49.21+/-8.46 ng/ml/120 min; HP=41.75+/-10.54 ng/ml/120 min) or the second OGTT (SC=96.63+/-13.68 ng/ml/120 min; HP=92.77+/-17.44 ng/ml/120 min). The high protein diet group experienced a delayed glucose response for the first (SC=30 min at 112+/-7 mg/dl; HP=60 min at 101+/-5 mg/dl) and second OGTT (SC=15 min at 117+/-5 mg/dl; HP=60 min at 95+/-7 mg/dl). Body mass increased to the same extent in each diet group from the initial to final weighing (SC=159+/-2 g to 254+/-7 g; HP=157+/-2 g to 242+/-7 g). Despite a delay in peak glucose response, these findings suggest that glucose tolerance and body mass were neither adversely nor positively affected by a high protein diet.     

EPO对高脂喂养小鼠棕色脂肪组织PRDM16、FGF21表达及STAT3磷酸化水平的影响

目的：探索促红细胞生成素（EPO）对高脂饲料（HFD）喂养小鼠血糖和血浆胰岛素水平、胰岛素抵抗指数（HOMA-IR）、糖耐量,以及棕色脂肪组织中含PR结构域蛋白16（PRDM16）、信号转导与转录激活因子3（STAT3）磷酸化水平（p-STAT3/STAT3）、成纤维细胞生长因子21（FGF21）mRNA以及蛋白质表达的影响,为肥胖及其并发症的发生机制提供线索。方法：20只高脂饲料喂养的C57BL/6J雄性小鼠随机分为对照组（HFD-Con）和EPO组（HFD-EPO）,两组分别腹腔注射生理盐水和EPO（200 IU/kg）,每周3次,连续4周。4周后检测两组动物的体重、血糖与血浆胰岛素水平、HOMA-IR及糖耐量的变化;分别使用实时定量PCR法和Western blot法检测棕色脂肪组织中PRDM16、STAT3、FGF21 mRNA和蛋白质水平。结果：腹腔注射EPO 4周后,HFD-EPO组小鼠体重为（26.65±0.85）g,HFD-Con组体重为（31.50±1.60）g,P<0.01。HFD-Con组血糖为（91.06±9.86）mg/dl,HFD-EPO组为（62.79±8.09）mg/dl,P<0.01;HFD-EPO组小鼠血浆胰岛素水平为（10.56±1.06）μU/ml,HFD-Con组为（13.2±1.1）μU/ml,P<0.01。与HFD-Con组比较,HFD-EPO组的糖耐量水平显著改善,胰岛素抵抗指数下降;HFD-EPO组动物棕色脂肪组织中PRDM16、FGF21mRNA以及蛋白质表达,p-STAT/STAT3水平均显著增加,两组小鼠肝脏中FGF21 mRNA含量、血浆中FGF21含量无明显差异。结论：EPO可能通过增加棕色脂肪组织中PRDM16表达促进棕色脂肪组织的分化,降低高脂喂养小鼠的血糖水平、改善高脂喂养小鼠的糖代谢状态。     

Iodide-induced hypothyroidism in a patient with anorexia nervosa

A 39-year-old woman who had been suffering from anorexia nervosa was found to have hypothyroidism. Serum T4, free T4, T3, free T3 and TSH were 3.19 micrograms/dl, 0.5 ng/dl, 15.3 ng/dl, 1.2 pg/ml and 162.1 microU/ml, respectively. On careful questioning, she was found to have taken an iodine-rich diet. The serum iodine concentration was 122 micrograms/dl (normal: 4-9 micrograms/dl) and urinary iodide excretion was 13.05 mg/day (normal: less than 2 mg). After withdrawal of the iodine-rich diet, her serum T4 gradually increased and TSH returned to the normal range. She was diagnosed as having iodide-induced hypothyroidism. However, no significant elevation of serum T3 or free T3 was observed. Serum T4, free T4, T3, free T3 and TSH were 7.85 micrograms/dl, 0.8 ng/dl, 13.6 ng/dl, 4.3 pg/ml and 6.02 microU/ml, respectively. The iodide-perchlorate discharge test result was negative. These findings suggest that there exists some unknown mechanism by which a patient with anorexia nervosa may be sensitive to excess iodide. Furthermore, it is of interest to note that in a recovery phase from the hypothyroid state, normalization of serum T4 rather than T3 is well-correlated to TSH secretion.     

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.     

Decrease of erythropoietin level by human recombinant tumour necrosis factor alpha (hrec TNFalpha) in patients with advanced cancer

Anaemia is a frequent complication of chronic inflammation, infectious diseases and cancer. Inappropriate erythropoietin production is regarded as one of the main causative factors responsible for the occurrence of anaemia. The pathogenesis of TNFalpha induced-anaemia has not been fully clarified yet and its influence on hematopoiesis has been suggested. We performed a clinical study to access the influence of hrec TNFalpha administration on plasma EPO concentration and the degree of anaemia in patients with advanced solid tumours for whom no other kind of therapy but palliative treatment was available. All these patients exposed mild anaemia (HT 36.1 +/- 1.0%). Plasma EPO was estimated at 8 a.m. before and after 5 days of TNFalpha therapy with a dose of 75 pg/day iv (cycle I). Two weeks later plasma EPO was estimated again before and after 5 days of TNFalpha administration of a double dose (150 microg/day) (cycle II). The control group comprised 8 non-cancer patients (5M/3F, age 48.5 +/- 6yr) with the same degree of anaemia (HT 36 +/- 1.1%) due to haemorrhage. In the control group the plasma EPO level was significantly higher (54.2 +/- 8 mU/ml) than in cancer patients before cycle I (17.1 +/- 2.5 mU/ml) and II (14.6 +/- 3.8 mU/ml) respectively.TNF administration was followed by a significant decline of plasma EPO both after the first (17.1 +/- 2.5 vs 9.0 +/- 1.5 mU/ml) and second cycle (14.6 +/- 3.8 vs 8.4 +/- 2.0 mU/ml) of TNF treatment. CONCLUSIONS: Patients with solid cancer and mild anaemia are characterised by inappropriate low plasma EPO concentration. Therapy with TNFalpha exerts a suppressive effect on EPO secretion in these patients.     

Hypothalamic hypogonadism in congenital adrenal hypoplasia

Congenital adrenal hypoplasia (CAHP) in its X-linked form is associated with hypogonadotropic hypogonadism (HH). A 23 year old man with this disorder received substitution therapy with gluco- and mineralocorticoids starting one week after birth and, recently, pulsatile subcutaneous GnRH treatment via a miniature infusion pump with stepwise increasing doses from 50 to 200 ng/kg body weight/2 hours for a total of 394 days. Testosterone levels increased from prepubertal levels to 409 ng/dl after 2 weeks and to 626 ng/dl after 3 months of treatment. The results of pulsatile GnRH therapy in our patient prove the hypogonadotropic hypogonadism to be of hypothalamic origin. Pulsatile GnRH substitution is a successful therapeutic regimen in patients with CAHP leading to pituitary and gonadal maturation.     

Triphasic response of prostacyclin production in rabbit thoracic aorta in early atherosclerosis

Atherosclerosis was induced in male rabbits by administration of a 2% cholesterol diet for up to 18 weeks. The animals were assessed for aortic microsomal prostanoid synthesis, morphologic assessment and serum cholesterol levels. Serum levels of cholesterol increased from control values of 84 +/- 9 ng/dl to 1632 +/- 227 ng/dl at 2 weeks (20-fold increase), and 4859 +/- 829 ng/dl at 9 weeks (57-fold increase). Aortic microsomal prostacyclin synthesis fell significantly at 2 weeks of cholesterol feeding which predated the morphologic appearance of atherosclerotic plaque in the 7 week group. Aortic microsomal PGI2 synthesis significantly increased by 7 weeks and did not fall until the 18 week group when a highly significant increase in aortic plaque developed. These findings suggest a triphasic response of aortic PGI2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI2 could indicate replacement of normal endothelium by atherosclerotic plaque.     

Inhibition of hemopoiesis in murine marrow cell cultures by recombinant murine tumor necrosis factor alpha: evidence for long-term effects on stromal cells

The addition of recombinant murine tumor necrosis factor alpha (rmTNF-alpha) to serum-free methylcellulose cultures inhibited macrophage colony formation stimulated by purified colony stimulating factor-1 (CSF-1), recombinant granulocyte-macrophage-CSF (rmGM-CSF), and recombinant interleukin 3 (rmIl-3). The concentration of rmTNF-alpha inhibiting colony formation by 50% (IC50) was between 2 and 20 ng/ml. Erythroid colony formation in cultures with erythropoietin (EPO) alone or EPO, rmIl-3, and rmGM-CSF in combination were reduced to a much lesser extent. In established long-term marrow cultures (LTMC), addition of 20 and 200 ng/ml of rmTNF-alpha resulted in release of cells from the adherent layer during the first week. Treatment of cultures with rmTNF-alpha for 4 consecutive weeks led to prolonged inhibition of cell production lasting up to 8 weeks after cessation of treatment. One day after addition of a low dose of TNF (2 ng/ml), "fat" cells were no longer observed in the adherent layer. Our results indicate that TNF inhibition of hemopoiesis occurs both at the progenitor cell and stromal cell levels.     

Aldosterone and corticosterone in amniotic fluid during various stages of pregnancy

Concentrations of unconjugated aldosterone and corticosterone were measured in amniotic fluid (AF) at different stages of pregnancy. At 9–20 weeks gestation the mean AF level of aldosterone was 14.4±0.7 ng/dl, and of corticosterone 82.9±6.4 ng/dl. Both showed the same pattern during pregnancy, with a rise in AF levels in the last few weeks. At 28–40 weeks gestation the mean AF aldosterone level was 25.5±2.0 ng/dl and the mean AF corticosterone was 218.3±26.6 ng/dl.     

Serum concentrations of oestradiol and progesterone during the normal oestrous cycle and early pregnancy in the lion (Panthera leo)

During a 6-month study period weekly serum samples demonstrated 9 oestradiol surges above 14 pg/ml (range 19-108 pg/ml) among 3 lionesses isolated from male lions. Intervals between peaks ranged from 3 to 8 weeks. Progesterone surges of more than 17 ng/ml (range 17-282 ng/ml) and lasting for 2-6 weeks were recorded after 7 of the oestradiol peaks. Sexual behaviour correlated well with the oestradiol peaks. Except for cornification following oestradiol peaks, there was no obvious vaginal cytology pattern at other times of the cycle. Pregnancy occurred after a 12-h contact with a male during behavioural oestrus. During gestation (108 days) oestradiol values remained low, while progesterone was elevated to 49 ng/ml within 12 h after mating, reaching a peak of 143 ng/ml at the 4th week, and remaining elevated during the next 2 months.     

Antler cycle and endocrine parameters in male axis deer (Axis axis): seasonal levels of LH, FSH, testosterone, and prolactin and results of GnRH and ACTH challenge tests.

1. Antler cycles of six adult male axis deer of southern Texas were relatively well synchronized within the herd. The old antlers were cast from December to March and regenerated antlers polished between March and June. The rutting season occurred in June and July. 2. LH and FSH exhibited little seasonal variation (LH 0.7-1.3 ng/ml; FSH 32-65 ng/ml). Prolactin levels were lowest in December (20 ng/ml) and highest in June (115 ng/ml). Testosterone concentrations exhibited a distinct seasonal pattern: minimum in December (0.1 ng/ml) and maximum in May (1.75 ng/ml). 3. After GnRH challenge (100 micrograms given i.m. in November), maximal LH levels (reached 40-60 min after injection), varied from 7.7 to 11.2 ng/ml, and T levels varied from 1.3 to 1.6 ng/ml. 4. Twenty I.U. of ACTH (given in March), elevated cortisol levels from 4-8 micrograms/dl (pretreatment) to 16-21 micrograms/dl (140 min post-administration).     

Fatty liver and hyperlipidemia in IDDM (insulin-dependent diabetes mellitus) of streptozotocin-treated shrews

Severe IDDM (insulin-dependent diabetes mellitus) was produced in the musk shrew (Suncus murimus, Insectivora) by a high dose (a single intraperitoneal injection of 100 mg/kg Body Weight) of streptozotocin (STZ) injection. All shrews that were administered a high dose of STZ exhibited hyperglycemia (449 +/- 16 mg/dl vs 73 +/- 4 mg/dl in controls) and hypoinsulinemia(0.25 +/- 0.07 ng/ml vs 10.96 +/- 1.97 ng/ml in controls) with ketosuria 10 days after injection. Their livers were enlarged and exhibited ayellowish-brown color with marked triglyceride (TG) accumulation (63.25 +/- 7.10 mg/g Liver vs 2.11 +/- 0.19 mg/g Liver in controls). It is probable that the increased influx of fatty acids into the liver induced by hypoinsulinemia and the low capacity of excretion of lipoprotein secretion from liver in the musk shrew resulting from a deficiency of apolipoprotein B synthesis play important roles in fatty liver formation. Hyperlipidemia was another feature in shrews with severe IDDM. The blood TG level was especially high in these shrews (899 +/- 178 mg/dl vs 23 +/- 5 mg/dl in controls). These results indicate that the IDDM shrew, induced by high doses of STZ, is a unique model characterized by fatty liver and hyperlipidemia and may be useful for studying lipid metabolism of IDDM.