Streptozotocin-induced Diabetic Female Rats Research Articles

Anti-diabetic impact of ‘Aju Mbaise’ herbal cocktail in streptozotocin-induced diabetic female rats

This study evaluated the hypoglycaemic potential of ‘Aju Mbaise’ herbal mixture. Female Wistar rats of 40 – 50 g and fifty-four (54) in number were obtained and housed at the animal house of the Department of Pharmacology, University of Port Harcourt. They were assembled into 6 groups of 9 rats each. Group I served as the normal control (NC) while the remaining five groups were induced with diabetes type 2 using high-fat diet (HFD) for about 8 weeks and streptozotocin at 35 mg/kg body weight. Group II was the diabetic control (DC) while the other groups (III, IV, V & VI) were administered 7.2 mg/kg metformin and the cocktail extract at three different concentrations of 500 mg/kg, 250 mg/kg, and 100 mg/kg respectively. Biochemical tests were conducted after twelve weeks of treatment. The blood glucose concentration was estimated using the Accu-check glucometer and glucose strips while the rest biomarkers were analyzed using their specific test kits. Diabetes mellitus was confirmed after HFD and STZ administration. Result obtained showed that the normal and metformin control groups recorded significant (p<0.05) lower blood glucose, liver enzymes (AST, ALT, & ALP), urea, and creatinine, as well as higher total protein concentrations when compared to the diabetic control and treated groups. Also, significant (p<0.05) reduction in blood glucose, liver enzymes, urea, and creatinine, as well as increase in total protein concentrations was recorded by the treated groups when compared to the diabetic control group. This study revealed the potential hypoglycaemic effect of ‘Aju Mbaise’ herbal cocktail.

Pregestational diabetes alters cardiac structure and function of neonatal rats through developmental plasticity

Pregestational diabetes (PGDM) leads to developmental impairment, especially cardiac dysfunction, in their offspring. The hyperglycemic microenvironment inside the uterus alters the cardiac plasticity characterized by electrical and structural remodeling of the heart. The altered expression of several transcription factors due to hyperglycemia during fetal development might be responsible for molecular defects and phenotypic changes in the heart. The molecular mechanism of the developmental defects in the heart due to PGDM remains unclear. To understand the molecular defects in the 2-days old neonatal rats, streptozotocin-induced diabetic female rats were bred with healthy male rats. We collected 2-day-old hearts from the neonates and identified the molecular basis for phenotypic changes. Neonates from diabetic mothers showed altered electrocardiography and echocardiography parameters. Transcriptomic profiling of the RNA-seq data revealed that several altered genes were associated with heart development, myocardial fibrosis, cardiac conduction, and cell proliferation. Histopathology data showed the presence of focal cardiac fibrosis and increased cell proliferation in neonates from diabetic mothers. Thus, our results provide a comprehensive map of the cellular events and molecular pathways perturbed in the neonatal heart during PGDM. All of the molecular and structural changes lead to developmental plasticity in neonatal rat hearts and develop cardiac anomalies in their early life.

Hypothalamic KNDy neuron expression in streptozotocin-induced diabetic female rats.

Kisspeptin neurons, i.e. KNDy neurons, in the arcuate nucleus (ARC) coexpress neurokinin B and dynorphin and regulate gonadotropin-releasing hormone/luteinizing hormone (LH) pulses. Because it remains unclear whether these neurons are associated with reproductive dysfunction in diabetic females, we examined the expression of KNDy neurons detected by histochemistry in streptozotocin (STZ)-induced diabetic female rats 8 weeks after STZ injection. We also evaluated relevant metabolic parameters – glucose, 3-hydroxybutyrate, and non-esterified fatty acids – as indicators of diabetes progression. Severe diabetes with hyperglycemia and severe ketosis suppressed the mRNA expression of KNDy neurons, resulting in low plasma LH levels and persistent diestrus. In moderate diabetes with hyperglycemia and moderate ketosis, kisspeptin-immunoreactive cells and plasma LH levels were decreased, while the mRNA expression of KNDy neurons remained unchanged. Mild diabetes with hyperglycemia and slight ketosis did not affect KNDy neurons and plasma LH levels. The number of KNDy cells was strongly and negatively correlated with plasma 3-hydroxybutyrate levels. The vaginal smear analysis showed unclear proestrus in diabetic rats 3–5 days after STZ injection, and the mRNA expression of kisspeptin in the ARC was decreased 2 weeks after STZ injection in severely diabetic rats. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV), which induce an LH surge, were unaffected at 2 and 8 weeks after STZ injection regardless of the diabetes severity. These results suggest that diabetes mellitus progression in females may negatively affect ARC kisspeptin neurons but not AVPV kisspeptin neurons, implicating a potential role of ARC kisspeptin neurons in menstrual disorder and infertility.

The potential role of male bone marrow mesenchymal stem cells of diabetic female rats

Background: Diabetes Mellitus is a metabolic defect that has the ability to produce an irreversible injury, abnormality of function and defect of several organs. Stem cell treatment posses a fantastic hope for the remedy damaged tissues or organs, and it is one of the utmost hopeful remedy for diabetic people. Thus, the current research direct to highlights of the potency function of MSCs of diabetic female rats. Methodology: Male albino bone marrow mesenchymal stem cells have been isolated and confirmed by their adhesion, spindle shape and also by cluster differentiation marker. Streptozotocin-induced diabetic female rats were intravenous injected by 1 x 105 MSCs (cell/rat). Results: MSCs group is capable of lowering blood glucose level, the activities of α-amylase, and S. L-MDA. However, hepatic glycogen contents showed an incredible increase when compared with the STZ-diabetic female nontreated rats. The histopathological and immuno-histochemical photo results confirmed that MSCs group noteworthy diminutive the degenerative alteration in pancreatic β-cells islet. Conclusions: Using bone marrow MSCs in remedy of STZ-diabetic female rats have the ability to recover odd biochemical parameters to normal or near normal level in STZ-induced diabetes model. But, MSCs needs more research and it may be more effective by injection more than one dose.

Previous Exercise Training Reduces Markers of Renal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Female Rats.

The aim of this study is to evaluate the effects of regular moderate exercise training initiated previously or after induction of diabetes mellitus on renal oxidative stress and inflammation in STZ-induced diabetic female rats. For this purpose, Wistar rats were divided into five groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD), and previously trained diabetic (PTD). Only the PTD group was submitted to treadmill running for 4 weeks previously to DM induction with streptozotocin (40 mg/kg, i.v). After confirming diabetes, the PTD, TD, and TC groups were submitted to eight weeks of exercise training. At the end of the training protocol, we evaluated the following: glycosuria, body weight gain, plasma, renal and urinary levels of nitric oxide and thiobarbituric acid reactive substances, renal glutathione, and immunolocalization of lymphocytes, macrophages, and nuclear factor-kappa B (NF-κB/p65) in the renal cortex. The results showed that exercise training reduced glycosuria, renal TBARS levels, and the number of immune cells in the renal tissue of the TD and PTD groups. Of note, only previous exercise increased weight gain and urinary/renal NO levels and reduced NF-κB (p65) immunostaining in the renal cortex of the PTD group. In conclusion, our study shows that exercise training, especially when initiated previously to diabetes induction, promotes protective effects in diabetic kidney by reduction of renal oxidative stress and inflammation markers in female Wistar rats.

Low-power laser irradiation in salivary glands reduces glycemia in streptozotocin-induced diabetic female rats.

Low-power laser irradiation (LPLI) has been extensively employed to modulate inflammation in vitro and in vivo. Previous reports from our group indicated that LPLI might regulate glycemia in diabetic animals. Diabetes results in chronic hyperglycemia and therefore chronic inflammation by upregulation of inflammatory markers such as the high mobility group box 1 (HMGB1) protein. Thus this study aimed to analyze the LPLI effects upon blood glucose levels, plasma insulin and HMGB1 concentrations in a diabetes experimental rat model. Streptozotocin-induced diabetic rats were irradiated in the salivary glands area with a diode laser applied at 660nm, 70mW, 20J/cm2 , 22.4J, with a spot area of 0.028cm2 and its effects were evaluated. LPLI significantly reduced diabetic rat hyperglycemia, without changing insulin or HMGB1 plasma levels, but possibly by ameliorating the insulin resistance in these animals. These findings suggest that LPLI might have a systemic effect, but more studies are necessary to better understand its mechanisms. Fasting blood glucose measured by peroxidase-glucose oxidase (PGO) method (A), showing a reduction of diabetic animals glycemia after LPLI. LPLI probably reduced the hyperglycemia in diabetes by improving the insulin resistance in these animals (B). C n=10, CL n=10, D n=7 and DL n=8. Data are expressed as mean ± SD; * P <0.05 vs. respective control group; # P<0.05 vs. D group.

Effects of Caffeine Administration on Brain Sodium-Potassium ATPase Activity in Healthy and Streptozotocin-Induced Diabetic Female Wistar Rats

Background: Diabetes mellitus affects the morphology and plasticity of the brain, leading to cognitive and electrophysiological impairment. We aim to determine effects of caffeine on brain Na+/K+-ATPase activity in streptozotocin-induced diabetic female rats. Methods: Female Wistar rats weighing about 180–200 g were used for the study and were divided into three study groups. Study groups A 1, 2, 3 were healthy rats administered 15, 20, 25 mg/kg caffeine intraperitoneally (i.p), respectively, for 5 weeks; study groups B 1, 2, 3 administered 15, 20, 25 mg/kg caffeine (i.p), respectively, for 5 weeks and maintained on caffeine for 3 weeks after diabetes induction; study groups C 1, 2, 3, were diabetic rats administered 15, 20, 25 mg/kg caffeine (i.p), respectively, for 3 weeks; control and diabetic untreated were administered normal saline. After administration, brains were homogenized in sucrose solution and kept at 4°C. Enzyme assay was conducted. Results: A significant (p < 0.05) decrease in Na+/K+-ATPas...

Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats.

This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney.

Exercise training attenuates acute hyperalgesia in streptozotocin-induced diabetic female rats

OBJECTIVES:We investigated the effects of chronic (eight weeks) low- to moderate-intensity swimming training on thermal pain sensitivity in streptozotocin-induced diabetic female rats.METHODS:Female Wistar rats (n = 51) were divided into the following groups: trained streptozotocin-induced diabetic rats [hyperglycemic trained (HT)], sedentary streptozotocin-induced diabetic rats [hyperglycemic sedentary (HS)], normoglycemic trained rats (NT) and normoglycemic sedentary rats (NS). Diabetes was induced by a single injection of streptozotocin (50 mg/kg, i.p.). One day after the last exercise protocol (60 min/day, five days/week for eight weeks) in the trained groups or after water stress exposure (ten min/twice a week) in the sedentary groups, the rats were subjected to a hot plate test.RESULTS:After eight weeks of swimming training, streptozotocin-induced diabetic rats presented a significantly lower body mass (trained: 219.5±29 g, sedentary: 217.8±23 g) compared with the normoglycemic groups (trained: 271±24 g, sedentary: 275.7±32 g). Interestingly, we did not find differences in blood glucose levels (mg/dl) between the trained and sedentary groups of the hyperglycemic or normoglycemic rats (HT: 360.2±66.6, HS: 391.7±66.7, NT: 83.8±14.0, NS: 77.5±10.1). In the hot plate test, the rats from the HT group presented a significantly lower latency than the other rats (HT: 11.7±7.38 s, HS: 7.02±7.38 s, NT: 21.21±7.64 s, NS: 22.82±7.82 s).CONCLUSION:Low-to-moderate swimming training for a long duration reduces thermal hyperalgesia during a hot plate test in streptozotocin-induced diabetic female rats.

Effect of estrogen on electroretinographic responses in streptozotocin-induced diabetic female rats

The aim of this study is to investigate the effects of estrogen on functional changes in the retinas of streptozotocin (STZ)-induced diabetic rats by using an electroretinography. Female rats were randomly divided into four treatment groups: (1) Control (sham operation and vehicle administration); (2) STZ (sham operation and STZ administration); (3) OVX (ovariectomy and vehicle administration); and (4) OVX + STZ (ovariectomy and STZ administration). Full-field electroretinograms (ERGs) were recorded before OVX and STZ administration and 4 and 12 weeks after STZ administration. At 4 weeks after STZ administration, although there were no differences in the STZ and OVX groups compared with the Control group, the amplitude of the cone-response was significantly lower in the OVX + STZ group than in the Control group (P = 0.013). At 12 weeks after STZ administration, this response showed a similar tendency in the STZ and the OVX + STZ groups. At 12 weeks after STZ administration, the implicit times of OP3 and OP4 and of the cone-response were significantly delayed in the STZ and OVX + STZ groups (OP3: P = 0.030 and 0.050, OP4: P = 0.0060 and 0.0053, cone-response: P = 0.014 and 0.039), compared with in the Control group. Thus, the retinal functions in STZ-induced diabetic female rats were aggravated by OVX. OVX-induced estrogen deficiency resulted in earlier changes in the amplitudes of cone-response, especially in the diabetes, although this is a transient effect and it is difficult to explain. Recognizing the early neurosensory change would enable a better understanding of the effect of estrogen in the retina.

Type 2 Diabetes Mellitus and Risk of Stress, Urge and Mixed Urinary Incontinence

To improve the understanding of the etiological relation between type 2 diabetes and urinary incontinence, we examined associations between diabetes and urinary incontinence type in 71,650 women 37 to 79 years old in the Nurses' Health Study and the Nurses' Health Study II. From 1976 to 2000 in the Nurses' Health Study and 1989 to 2001 in the Nurses' Health Study II participants reported diagnoses of type 2 diabetes. Women with incident urinary incontinence at least weekly were identified from 2000 to 2002 in the Nurses' Health Study and 2001 to 2003 in the Nurses' Health Study II. We pooled data from the 2 cohorts, and estimated odds ratios and 95% confidence intervals using multivariable logistic regression adjusting for age, parity, body mass index, smoking, hysterectomy, functional limitations, menopausal status, postmenopausal hormone use, incontinence promoting medications and study cohort. The incidence of at least weekly urinary incontinence was 5.3% (3,612 of 67,984) among women without type 2 diabetes and 8.7% (318 of 3,666) among women with diabetes. Overall the multivariable adjusted odds of incident urinary incontinence were increased 20% (OR 1.2, 95% CI 1.0-1.3, p = 0.01) among women with vs without type 2 diabetes. This increase appeared largely explained by significantly greater odds of urge urinary incontinence (OR 1.4, 95% CI 1.0-1.9, p = 0.03). There was no apparent association between diabetes and stress (p = 0.3) or mixed (p = 0.6) urinary incontinence, although confidence intervals were somewhat wide. Our findings suggest that type 2 diabetes may especially influence urge urinary incontinence. Further research is needed to confirm this finding and identify pathways linking these conditions.

Perturbation of 11-eicosenoate metabolism in female diabetic rats

Considering the proposed preventive effect of nervonic acid on obesity- and diabetes-related coronary risk factors, the content of its precursors (oleic, 11-eicosenoic and 13-docosenoic acids) was measured in liver and plasma phospholipids and triglycerides, brain and spleen phospholipids, and adipose tissue lipids of fed or overnight fasted control and hereditarily diabetic Goto-Kakizaki female rats, as well as fed streptozotocin-induced diabetic female rats. In liver and brain phospholipids, the 11-eicosenoate/oleate ratio was significantly higher in diabetic rats than in control animals. Such was not the case in either spleen phospholipids or liver triglycerides and adipose tissue lipids. The increase in the liver phospholipid 11-eicosenoate/oleate ratio found in female diabetic rats represents a mirror image of the situation recently documented, in the same animal models of diabetes, in male rats. These contrasting findings may be relevant to the higher coronary heart disease risk prevailing in female, as compared to male, diabetic subjects.

Effect of spray-dried ethanolic extract ofAndrographis paniculata(Burm. F.) Nees on streptozotocin-induced diabetic female rats

Effect of spray-dried ethanolic extract of<i>Andrographis paniculata</i>(Burm. F.) Nees on streptozotocin-induced diabetic female rats

Ultra-structural morphological abnormalities of the urinary bladder in streptozotocin-induced diabetic female rats

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction.

옥천산이 당뇨 쥐의 혈당, 지질 및 단백질 농도에 미치는 영향

동의보감에서 소갈증에 응용되는 옥천산 분말이 당뇨 암쥐의 혈당, 혈청과 간의 지질 및 단백질 농도에 미치는 영향을 조사하고자, 평균체중 313.6±18.5 g되는 Spraque-Dawley계 암쥐를 정상군, 당뇨 대조군 및 당뇨 옥천산군 등 3군으로 나누어 각 실험식이로 5주간 사육한 결과는 다음과 같다. 5주간 체중변화는 정상군은 3.5 g 증가하였으나, 당뇨 대조군과 당뇨 옥천산군은 당뇨로 인한 대사장애로 각각 97.8g 과 99.1 g씩 체중이 감소되었다. 췌장의 무게는 정상군에 비하여 당뇨 대조군은 유의하게 증가되었으나 당뇨 옥천산군은 정상군과 비슷하였다. 비장의 무게는 정상군에 비하여 당뇨 대조군과 당뇨 옥천산군이 유의하게 감소하였다. 혈청의 중성지질, 총 콜레스테롤, LDL-콜레스테롤 및 간의 콜레스테롤 농도는 당뇨 옥천산군이 당뇨 대조군보다 유의하게 감소되어 정상군과 비슷한 수준을 보였다. HDL-콜레스테롤 농도와 HDL-콜레스테롤/총 콜레스테롤의 비율은 정상군과 당뇨 실험군들이 비슷한 수준을 보였다. 동맥경화지수 및 혈당량은 정상군에 비하여 당뇨 실험군들이 증가하였다. 간의 총 지질 및 중성지질 농도는 정상군에 비하여 당뇨 대조군과 당뇨 옥천산군이 유의하게 감소되었다. 혈청의 단백질과 알부민농도는 정상군에 비하여 당뇨 대조군과 당뇨 옥천산군이 유의하게 감소되었다. 이상의 결과로 보아 당뇨 쥐에 옥천산 분말이 혈당 및 동맥경화지수를 낮추는 효과는 없었으나, 혈청의 중성지질, 총 콜레스테롤, LDL-콜레스테롤 및 간의 콜레스테롤 농도를 낮추는 효과가 나타났다.

Myocardial and Hepatic Free Carnitine Concentrations in Pups of Diabetic Female Rats

Background/Aims: Adequate carnitine levels are required for normal fatty acid and energy metabolism in heart muscle. It is well known that streptozotocin-induced diabetic rats develop myocardial carnitine deficiency and that carnitine therapy may be beneficial to the diabetic heart. Infants of diabetic mothers (IDM) are known to be at risk for developing a hypertrophic type of cardiomyopathy. In the present investigation, we examined the free carnitine concentration from cardiac and hepatic tissue in pups of streptozotocin-induced diabetic female rats. We also assessed the effect of maternal L-carnitine supplementation on the free carnitine concentration in pups of diabetic rats. Method: Three groups, each consisting of 4 Wistar albino female rats, were studied, Group 1 (untreated diabetic; n = 4) and group 2 (L-carnitine-treated diabetic; n = 4) rats were given streptozotocin (60 mg/kg) by intraperitoneal injection; group 3 were controls. During pregnancy, L-carnitine was given at a dose of 150 mg/kg by intraperitoneal injection once a day for 14 days. Cesarean section was carried out, and 113 newborn rats (group 1 n = 36; group 2 n = 38; group 3 n = 39) were obtained from all the pregnant rats. Results: The free carnitine concentration in myocardial tissue was significantly decreased in the female diabetic rats (p < 0.001). However, the free carnitine concentration from hepatic tissue in diabetic female rats was similar to that in controls. In pups of group 1 diabetic rats, a significantly decreased free carnitine concentration was found in both myocardial and hepatic tissue compared to group 2 and controls. The free carnitine content from myocardial and hepatic tissue was significantly elevated in the maternal L-carnitine-supplemented group when compared to group 1 and control pups (p < 0.001 and p < 0.05, respectively). Conclusions: The present study has demonstrated that the free carnitine concentration from myocardial and hepatic tissue is significantly reduced in pups of streptozotocin-induced diabetic female rats. This study has also shown that administration of maternal L-carnitine improves the carnitine level in pups of diabetic rats. A decreased myocardial carnitine concentration may be partly responsible for the development of cardiomyopathy in IDM.

The Hypothalamic-Pituitary Axis of Streptozotocin-Induced Diabetic Female Rats is Not Normalized by Estradiol Replacement*

Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes. The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2). Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups. Diabetes was induced with an injection of streptozotocin in the D and DI groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH was assessed in C and D animals. Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were also reduced in D vs. C animals despite comparable estrogen therapy (P less than 0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001). D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state. These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.

The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin

When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemolobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normla estrous cycles, and hepatic IGF-I mRNA (8.94 ± 1.02 O.D. units per μg total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 ± 0.91 and 17.15 ± 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 ± 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 ± 23.1 ng/ml), non-diabetic diestrous rats (165 ± 18.4 ng/ml) and untreated diabetic rats (135 ± 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 ± 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin theraphy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrous groups.

The cardiomyopathy in infants of streptozotocin-induced diabetic female rats.

Transient hypertrophic cardiomyopathy has been described in human infants of diabetic mothers. The purpose of this study was twofold: first, to document the features of cardiac hypertrophy in newborns of female rats with streptozotocin-induced diabetes and second, to investigate the natural history of this cardiomyopathy. Marked asymmetrical septal hypertrophy with hypertrophy of myocytes was observed in newborns of diabetic female rats, whether or not the mothers received daily administration of NPH insulin. The abnormal cardiac morphology was no longer apparent 4 weeks after birth. Thus, in this model, the asymmetrical septal hypertrophy was secondary and was not a manifestation of genetically transmitted hypertrophic cardiomyopathy.