Zinc and insulin metabolism

A review of experimental studies of the effect of zinc nutrition on insulin metabolism is presented. In addition to a short introduction to the synthesis, secretion, and action of insulin, the effects of zinc deficiency—specifically on glucose tolerance, insulin secretion, insulin synthesis and storage, and on total insulin-like activity—are dealt with. The concentrations of zinc and chromium in serum, pancreas, and liver are compared to those of zinc-deficient animals and pair-fed controls. In contrast to pair-fed controls, zinc-deficient rats had unaltered proinsulin contents after glucose stimulation, but they showed a diminished glucose tolerance, lowered serum insulin content, and an elevated total insulin-like activity. The serum zinc concentration of the deficient animals was greatly reduced and did not change during glucose stimulation, whereas it rose in the case of the pair-fed controls. The serum chromium concentration increased in both groups in response to glucose stimulation. In the pancreas of the deficient animals, the zinc concentration was reduced 60% and it increased during the glucose tolerance test. In the liver there were no significant differences. The chromium concentrations were elevated in both the pancreas and liver of the zinc-deficient rats by 60 and 100%, respectively, and were not influenced by glucose injection. These studies show clearly that nutritional zinc deficiency influences insulin metabolism and action.     

Improvement of high fat-diet-induced insulin resistance in dipeptidyl peptidase IV-deficient Fischer rats

F344/DuCrj rats are genetically deficient in dipeptidyl peptidase IV (DPPIV). This enzyme degrades glucagon-like peptide-1 (GLP-1), which induces glucose-dependent insulin secretion. Glucose tolerance of F344/DuCrj rats is improved as a result of enhanced insulin release induced by high levels of plasma GLP-1. In this study, we fed F344/DuCrj rats and DPPIV-positive F344/Jcl rats, aged five weeks, on a high-fat (HF) diet to examine the effect of DPPIV deficiency on food intake and insulin resistance. F344/Jcl rats gained significantly more body weight and consumed significantly more food than F344/DuCrj rats from Week 4 on either control or HF diet. Glucose excursion in the oral glucose tolerance test (OGTT) was improved in F344/DuCrj rats fed on the control or HF diet at all times examined, compared with F344/Jcl rats. Homeostasis model assessment (HOMA) insulin resistance values of F344/DuCrj and F344/Jcl rats fed on HF diet were higher than those of animals fed on control diet up to Week 6. However, HOMA insulin resistance values of F344/DuCrj rats fed on HF diet became significantly lower than those of F344/Jcl rats on HF diet during Weeks 8-10. The area under the insulin curve in the OGTT at Week 10 showed that the insulin resistance of HF-diet-fed F344/DuCrj rats was greatly ameliorated. Plasma active GLP-1 concentrations of F344/DuCrj rats in the fed state were significantly higher than those of F344/Jcl rats. These observations suggest that DPPIV deficiency results in improved glucose tolerance and ameliorated insulin resistance owing to enhanced insulin release and inhibition of food intake as a result of high active GLP-1 levels.     

Effects of antidiabetic drugs on glucose tolerance in streptozotocin-nicotinamide-induced mildly diabetic and streptozotocin-induced severely diabetic mice

In this study, streptozotocin-nicotinamide-induced mildly diabetic mice and streptozotocin-induced severely diabetic mice were created to compare their characteristics and to investigate the effects of antidiabetic drugs on glucose tolerance. In severely diabetic mice, the pancreatic insulin content decreased to approximately 10% of levels found in normal mice. These mice also showed a decrease in body weight, a marked increase in nonfasting blood glucose levels and urinary glucose excretion, and a marked decline in glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in mildly diabetic mice. These mice did not show any change in body weight, but displayed a mild increase in nonfasting blood glucose levels and urinary glucose excretion, and a mild decline in glucose tolerance due to loss of early-phase insulin secretion. Administration of antidiabetic drugs, namely voglibose, metformin, glibenclamide, sitagliptin and insulin, significantly improved glucose tolerance in mildly diabetic mice. In severely diabetic mice, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results demonstrate that streptozotocin-nicotinamide-induced mildly diabetic mice have many pathological features resembling type 2 diabetes, and can serve as models for the pharmacological evaluation of many antidiabetic drugs.     

Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism

To clarify mechanism behind the abnormal glucose tolerance, observed in hyperthyroidism, we studied genomic and nongenomic effects of thyroid hormone on insulin secretion using a rat model of hyperthyroidism. Male Sprague-Dawley rats were intraperitoneally injected with vehicle, low (100 microg/kg) or high dose (600 microg/kg) of thyroxin (T(4)) for 2 weeks. Rats treated with high dose, but not low dose, of T(4), showed an increase in serum T(3) levels, and a decrease in body weight as compared to control rats. In rats treated with either dose of T(4), fasting blood glucose levels were increased, but serum insulin levels were similar to those of controls. After an oral glucose load, blood glucose levels were increased in rats treated with high dose, but not low dose, of T(4). Serum insulin levels after the oral glucose load were decreased in rats treated with either dose of T(4). After an intravenous glucose load, blood glucose levels were comparable among groups, but serum insulin levels tended to be low in T(4)-treated rats. Steady-state blood glucose levels were comparable among groups. The insulin secretory responses to high glucose (20mM) or arginine (10mM) of the isolated pancreas was decreased in rats treated with high dose, but not low dose, of T(4). Mean insulin secretory response to glucose and arginine were decreased by 40.1% and by 60.4% in high-dose-T(4)-treated rats. Addition of T(3) in the perfusion medium decreased glucose-induced insulin release. Ratios of proinsulin mRNA levels to beta-actin mRNA were decreased in the islets of T(4)-treated rats (0.45 +/- 0.07 vs control 0.61 +/- 0.03, p < 0.05). Levels of TR (thyroid hormone nuclear receptor) alpha1 + cErb Aalpha2 mRNA, but not TRbeta1, were decreased in the pancreatic islets of T(4)-treated rats. Calculated islet area was increased, but the number of beta-cells determined immunohistochemically was not increased in T(4)-treated rats, nor the volume density of insulin positive islets. We concluded that a deficient pancreatic beta-cell response to glucose, rather than insulin resistance, was responsible for abnormal glucose tolerance in this model of hyperthyroidism. Thyroid hormone causes a decrease in glucose-induced insulin secretion. We observed nongenomic and genomic effects of thyroid hormone on glucose-induced insulin secretion.     

Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide.

Serial oral glucose tolerance tests in rats treated with streptozotocin and nicotinamide showed that blood glucose levels after glucose loading were suppressed significantly 7 months after treatment as compared to those of earlier stages. Post-glucose plasma insulin levels were significantly elevated at the 9th to 12th month and concomitantly fasting plasma glucagon levels rose significantly. At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment. Post-glucose plasma glucagon levels, however, did not show remarkable changes throughout the observation. In spite of hyperinsulinemia, post-glucose plasma glucagon levels of tumor-bearing rats were significantly lower than those of body weight adjusted controls. It is inferred from the study that secretory activity of pancreatic A-cells of tumor-bearing rats is restrained by excess insulin released from islet cell tumors.     

Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats

We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0 microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.     

Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis

Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on glucose metabolism, we presently analyzed the effect of biotin deprivation on glucose homeostasis and on pancreatic islet morphology. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-deficient or a biotin-control diet (0 or 7.2 μmol of free biotin/kg diet, respectively) over a period of 8 weeks. We found that biotin deprivation caused reduced concentrations of blood glucose and serum insulin concentrations, but increased plasma glucagon levels. Biotin-deficient mice also presented impaired glucose and insulin tolerance tests, indicating defects in insulin sensitivity. Altered insulin signaling was linked to a decrease in phosphorylated Akt/PKB but induced no change in insulin receptor abundance. Islet morphology studies revealed disruption of islet architecture due to biotin deficiency, and an increase in the number of α-cells in the islet core. Morphometric analyses found increased islet size, number of islets and glucagon-positive area, but a decreased insulin-positive area, in the biotin-deficient group. Glucagon secretion and gene expression increased in islets isolated from biotin-deficient mice. Our results suggest that biotin deficiency promotes hyperglycemic mechanisms such as increased glucagon concentration and decreased insulin secretion and sensitivity to compensate for reduced blood glucose concentrations. Variations in glucose homeostasis may participate in the changes observed in pancreatic islets.     

Effects of age and anesthetic on plasma glucose and insulin levels and insulin sensitivity in spontaneously hypertensive and Wistar rats

We examined the effects of anesthetic, age, and strain on oral glucose tolerance tests (OGTT, 1 g/kg body weight) and intraperitoneal glucose tolerance tests (IPGTT, 2 g/kg body weight) in spontaneously hypertensive (SH) and Wistar rats. Pentobarbital anesthesia caused an elevation in basal glucose and insulin levels in Wistar rats at 9 and 16 weeks of age and in SH rats at 9 weeks. Anesthesia increased the insulin output during an OGTT in both strains of rats while glucose was unchanged. Anesthesia reduced the insulin sensitivity index calculated from the OGTT but not from the IPGTT data. The age of the rats (9-11 vs. 16-18 weeks) had no effect on the basal glucose or insulin levels, but older Wistar rats had a greater insulin output following oral glucose and older SH rats had a greater insulin output following intraperitoneal glucose. On the basis of the insulin sensitivity index, SH rats were clearly more insulin resistant than age-matched Wistar rats. The SH rats also had higher basal insulin levels, as well as higher insulin output, following both glucose challenges. In summary, SH rats are more insulin resistant than Wistar rats, and anesthesia, which elevated basal glucose and insulin levels and increased the insulin output in response to a glucose challenge, may increase insulin resistance.     

Carbohydrate metabolism in erythrocytes of copper deficient rats

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.     

Effects of deoxycorticosterone acetate on glucose metabolism in nondiabetic and streptozotocin-diabetic rats.

A previous study in our laboratory showed that streptozotocin (STZ) induced diabetic, deoxycorticosterone acetate (DOCA) induced hypertensive rats exhibited significantly lower levels of plasma glucose than did normotensive diabetic animals. The present experiments further investigate the effects of DOCA treatment on fasting levels of plasma glucose and insulin and on their changes after oral glucose challenge in nondiabetic and STZ-diabetic rats. It was found that, in nondiabetic rats, DOCA-induced hypertension was associated with normal glucose levels and glucose tolerance but with significantly lower levels of plasma insulin. DOCA-treated diabetic animals showed significantly lower levels of plasma glucose, but their plasma insulin concentrations were not significantly different from those of the DOCA vehicle treated diabetic rats. DOCA-treated diabetic rats also had significantly higher plasma levels of cholesterol and triglycerides. It is suggested that DOCA may have a direct or indirect action on the assimilation, production, or utilization of glucose, perhaps leading to an improvement in insulin sensitivity and subsequently a decrease in insulin secretion.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin and glucagon relationships during aging in rats.

Oral glucose tolerance tests were performed under pentobarbital anesthesia in 43 male Wistar rats 2 to 18 months of age in order to determine if insulin and glucagon secretion are altered with aging. Although any linear correlation was not demonstrated between aging and blood glucose, plasma insulin or glucagon levels, post-glucose levels of blood glucose were significantly suppressed and those of plasma glucagon were significantly elevated at 4 to 6 months of age. No significant difference was found between young (2 months of age) and aged rats (12 to 14 and 17 to 18 months of age) in either blood glucose or plasma insulin levels during oral glucose load. On the other hand, post-glucose plasma glucagon levels of the aged rats were significantly higher than those of the young ones. Furthermore, comparisons of various kinds of indices among the different age groups, such as insulinogenic index, insulin/glucagon and so forth during oral glucose tolerance tests also indicate the significant alteration of glucagon secretion during aging process. It is concluded from the present data that glucose tolerance does not apparently deteriorate during aging process in rats but that glucagon responses to oral glucose administration are elevated with aging.     

Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance

Fructose feeding induces moderate increases in blood pressure levels in normal rats, which is associated with hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Increased vascular resistance, sodium retention, and sympathetic overactivity have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid, has been reported to have antihypertensive and sympatholytic actions. In the present study, the effects of taurine on blood pressure, plasma levels of glucose and insulin, glucose tolerance, and renal function were studied in fructose-fed rats. Fructose-fed rats had higher blood pressure and elevated plasma levels of insulin and glucose. The plasma glucose levels were higher in fructose-fed rats than in controls at 15, 30, and 60 min after the oral glucose load. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and attenuated the hyperinsulinemia in fructose-fed rats. The exaggerated glucose levels in response to the oral glucose load was also prevented by taurine administration. Thus, taurine supplementation could be beneficial in circumventing metabolic alterations in insulin resistance.     

Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets

Despite documented studies, the exact role of stress on diabetes is still unclear. The present study investigates the effect of chronic psychological stress on insulin release from isolated rat pancreatic islets. Male Wistar rats were divided into two groups of control and stressed (n=8/group). The animals of the stressed group were exposed to restraint stressors (1 h twice daily) for 15 or 30 consecutive days. At the beginning and end of the experimental periods, the animals were weighed and blood samples taken to determine the fasting plasma levels of glucose, insulin and corticosterone. On the following day the pancreatic islets of 5/group of the above animals were isolated and the static release of insulin in the presence of different glucose concentrations (2.8, 5.6, 8.3, 16.7 mM) was assessed. The results showed that in the stressed group, fasting plasma glucose levels were increased significantly on the 15th day as compared to the control group. However there was no significant increase on the 30th day. Fasting plasma insulin was significantly decreased on the 15th and 30th days of the experiment in the stressed group. Stressed rats showed significantly higher fasting plasma corticosterone levels, only on the 15th day, as compared to the control rats. In response to increasing concentrations of glucose, insulin release from islets of the stressed group was increased significantly on the 30th day of the experiment as compared to the control group. We conclude that chronic psychological stress could increase responsiveness of pancreatic beta cells to glucose, in vitro, and thus, low insulin levels of the stressed animals, in vivo, may be due to reason(s) other than the reduction of insulin releasing capacity of pancreatic beta cells.     

Effects of an olive oil-enriched diet on glucagon-like peptide 1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in an animal model of type 2 diabetes.

In the light of a recent study conducted in normal rats, the present investigations were aimed at exploring the immediate and long-term effects of an olive oil-enriched diet (OO diet) on GLP-1 release and intestinal content, plasma insulin concentration, glucose tolerance and pancreatic insulin content in adult rats that had been injected with streptozotocin during the neonatal period (STZ rats). The OO diet, when compared to a standard diet, increased the immediate GLP-1 response in meal-trained rats, but decreased GLP-1 content in the intestinal tract after 50 days. Over 50 days, the body weight gain was lower in the rats fed the OO diet compared to standard diet. In the former, however, no improvement of glucose tolerance or insulin response during an oral glucose tolerance test was observed. Thus, a paradoxical lowering of the insulinogenic index, i. e. the paired ratio between plasma insulin and glucose concentration, was recorded during the oral glucose tolerance test in rats fed either standard or OO diet. Moreover, the insulin content of the pancreas was equally low in the STZ rats fed either standard or OO diet. These findings will be discussed in the framework of possible differences in the pathophysiology of B-cell dysfunction in most patients with type-2 diabetes and the present animal model of non-insulin-dependent diabetes.     

The effect of variable magnesium intake on potential factors influencing endurance capacity

Rats fed a magnesium (MG) deficient diet have a lower endurance capacity than rats fed Mg adequate diets. The current study evaluates the effects of marginal, moderate, and severe Mg deficiencies on physiological and biochemical changes that may contribute to the reduced endurance capacity of Mg deficient rats. Variable levels of dietary Mg (400, 200, 100, 50 μg/g) were fed for 23 d to 5-wk-old male Osborne-Mendel rats. Indirect blood pressure and heart rate were measured during dietary treatment. Forty-eight hours after an endurance test, rats were killed and sampled for plasma glucose, insulin, and triglyceride levels. Organ weights, mineral and trace element concentrations, and carcass composition were determined. Blood pressure was lower in rats fed 50 and 100 ppm Mg during the first half of the study than in controls (400 ppm Mg). There were no significant differences in blood pressure among groups at the end of the study. Heart rate was not affected by dietary Mg intake. Plasma insulin was lowered by decreasing dietary Mg; however, plasma glucose and triglyceride concentrations were not affected by dietary Mg intake. Rats fed 100 and 50 ppm Mg diets had significantly higher calcium concentrations in plasma and gastrocnemius muscle than controls. Dietary Mg variably affected tissue trace element (iron, zinc, copper, and manganese) concentrations but did not affect Mg concentrations in any organ studied. Body composition was significantly altered by dietary Mg intake. In conclusion, variable Mg intake differentially affects the parameters evaluated. Thus, the decreased endurance capacity of the Mg deficient rat is apparently not the result of a single biochemical lesion but is likely to be multifactorial.     

Growth hormone,insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.     

阿司匹林增加胰岛素抵抗大鼠胰岛素敏感性的实验研究

目的　观察阿司匹林对高脂饮食大鼠胰岛素敏感性的影响。方法　灌服阿司匹林前后采用腹腔注射胰岛素耐量试验 (IITT)观察大鼠胰岛素的敏感性 ,并测定空服胰岛素、血糖和血脂等。结果　高脂饮食 4月、阿司匹林治疗 4周后 ,IITT发现高脂组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著高于正常对照组 (P <0 0 5或P <0 0 1 ) ;而阿司匹林治疗组腹腔注射胰岛素后 1h、1 5h和 2h的血糖及空腹胰岛素和甘油三酯水平显著低于高脂组 (P <0 0 5或P <0 0 1 ) ,与正常对照组差异无显著性。结论　大剂量阿司匹林有增加胰岛素敏感性和改善脂代谢紊乱的作用     

Vitamin D Supplementation Modulates Blood and Tissue Zinc, Liver Glutathione and Blood Biochemical Parameters in Diabetic Rats on a Zinc-Deficient Diet

Previous studies suggest a protective effect of vitamin D3 on zinc deficiency-induced insulin secretion and on pancreas β-cell function. The aim of this study was to investigate the effect of vitamin D on blood biochemical parameters, tissue zinc and liver glutathione in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin D3 for 27 days. At the end of the experiment, blood, femur, pancreas, kidney and liver samples were taken from all rats. The serum, femur, pancreas, kidney and liver zinc concentrations, liver glutathione, serum alkaline phosphatase activity, daily body weight gain and food intake were lower in the zinc-deficient rats in comparison with those receiving adequate amounts of zinc. These values were increased in the zinc-deficient group that was supplemented with vitamin D3. The serum total cholesterol, triglycerides, total protein, urea, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and blood glucose values were higher in rats fed a zinc adequate diet, but their concentrations were decreased by vitamin D3 supplementation. The serum total protein levels were not changed by zinc deficiency and vitamin D3 supplementation. These results suggest that vitamin D3 modulates tissue zinc, liver glutathione and blood biochemical values in diabetic rats fed a zinc-deficient diet.