EFFECTS OF THE PITUITARY GROWTH AND ADRENOCORTICOTROPIC HORMONES ON THE URINARY GLUCOSE, NITROGEN AND KETONE BODIES OF DIABETIC RATS MAINTAINED ON A CARBOHYDRATE-FREE DIET

The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat.

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Lipogenesis from ketone bodies in perfused livers from streptozocin-induced diabetic rats

Diabetes ◽

10.2337/diabetes.37.1.50 ◽

1988 ◽

Vol 37 (1) ◽

pp. 50-55 ◽

Cited By ~ 3

Author(s):

L. E. Freed ◽

G. Endemann ◽

J. F. Tomera ◽

V. C. Gavino ◽

H. Brunengraber

Keyword(s):

Ketone Bodies ◽

Diabetic Rats

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Uptake of Ketone Bodies in Perfused Hindquarter and Kidney of Starved, Thyrotoxic, and Diabetic Rats

Experimental Biology and Medicine ◽

10.3181/00379727-203-43572 ◽

1993 ◽

Vol 203 (1) ◽

pp. 55-59 ◽

Cited By ~ 1

Author(s):

T. Ikeda ◽

M. Ishimura ◽

H. Terasawa ◽

H. Ochi ◽

I. Ohtani ◽

...

Keyword(s):

Ketone Bodies ◽

Diabetic Rats

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Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats

Acta Endocrinologica ◽

10.1530/eje.0.1340459 ◽

1996 ◽

Vol 134 (4) ◽

pp. 459-466 ◽

Cited By ~ 18

Author(s):

Parri Wentzel ◽

Ulf J Eriksson

Keyword(s):

Glucose Concentration ◽

Insulin Treatment ◽

Ketone Bodies ◽

Diabetic Rats ◽

Normal Serum ◽

Serum Factors ◽

Crown Rump Length ◽

Increased Risk ◽

Control Serum ◽

Teratogenic Potential

Wentzel P, Eriksson UJ. Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats. Eur J Endocrinol 1996;134:459–66. ISSN 0804–4643 Maternal diabetes during pregnancy constitutes an increased risk for congenital malformations in the offspring. Previous studies have identified several serum components with teratogenic activity, e.g. glucose and β-hydroxybutyrate, but have also suggested that the teratogenic influence of the diabetic environment on the developing embryo is multifactorial and may depend upon changed concentrations of several maternal metabolites. In the present investigation we aimed to assess the teratological impact of small, concomitant alterations in a series of metabolites, particularly those not previously identified as teratogens. We thus investigated the influence of a mild diabetic environment by culturing gestational day-9 rat embryos in serum from insulin-treated diabetic rats for 48 h in vitro, and compared the embryonic outcome with that obtained after culture in normal serum and in serum from manifestly diabetic rats without insulin treatment. The glucose concentration was adjusted to 10 or 30 mmol/l in the cultures, and the embryos were evaluated with respect to crown–rump length, protein and DNA content, number of somites and malformation score (comparing major, minor or no malformations). We found that increased glucose levels caused embryonic maldevelopment in both normal and diabetic serum, and that despite normalization of the diabetic state, the serum from the insulin-treated diabetic rats caused more growth retardation than the nondiabetic control serum. The normalized diabetic serum was also more teratogenic than the normal serum at the low glucose concentration, whereas the serum from the manifestly diabetic rats tended to cause more dysmorphogenesis at 30 mmol/l glucose than both the normal and normalized diabetic serum. The results suggest that the teratogenicity of maternal serum in diabetic pregnancy is not mediated exclusively by increased concentrations of glucose and ketone bodies. The efforts to diminish the teratogenic effects of a diabetic environment should therefore include normalization of a multitude of serum factors, including glucose and ketone bodies. Parri Wentzel, Department of Medical Cell Biology, University of Uppsala, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden

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Anti-hyperglycaemic effects of dioxidovanadium complex cis-[VO2(obz)py] avert kidney dysfunction in streptozotocin-induced diabetic male Sprague–Dawley rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0278 ◽

2021 ◽

pp. 1-9

Author(s):

Bonisiwe Mbatha ◽

Andile Khathi ◽

Ntethelelo Sibiya ◽

Irvin Booysen ◽

Patrick Mangundu ◽

...

Keyword(s):

Blood Glucose ◽

Kidney Injury ◽

Diabetic Control ◽

Positive Control ◽

Diabetic Rats ◽

Vanadium Complex ◽

Sprague Dawley ◽

Kidney Dysfunction ◽

Urinary Glucose ◽

Blood Glucose Concentrations

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis-[VO2(obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis-[VO2(obz)py] (40 mg·kg–1) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the anti-hyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes.

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Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rats: Relation to severity of diabetes

Acta Endocrinologica ◽

10.1530/acta.0.1220374 ◽

1990 ◽

Vol 122 (3) ◽

pp. 374-378 ◽

Cited By ~ 38

Author(s):

Allan Flyvbjerg ◽

Hans Ørskov

Keyword(s):

Blood Glucose ◽

Growth Factor ◽

Experimental Diabetes ◽

Diabetic Rats ◽

Renal Hypertrophy ◽

Kidney Weight ◽

Factor I ◽

Urinary Glucose ◽

Igf I ◽

Growth Factor I

Abstract The initial renal hypertrophy in experimental diabetes is dependent on the prevailing blood glucose level and is associated with renal accumulation of insulinlike growth factor I. To investigate the relationship of blood glucose to kidney IGF-I, a graded range of diabetic aberration was established in young rats by iv injection of increasing amounts of streptozotocin (25–80 mg/kg) at day 0. In 30 diabetic rats the mean of day 1 and day 2 blood glucose concentrations ranged from 6.2 to 32.0 mmol/l and 24-h urinary glucose excretion (24–48 h) from 0.04 to 43.3 mmol/24 h. The right kidneys were removed after 48 h, weighed and their IGF-I concentration analysed by radioimmunoassay. Kidney IGF-I was positively correlated to blood glucose (r = 0.66, p<0.0001) as well as to 24-h urinary glucose output (r = 0.54, p<0.005). At this early stage, kidney weight already correlated to blood glucose (r = 0.60, p<0.0005). No relationship between kidney IGF-I and kidney weight was found. However, if animals with severe diabetes were excluded, a significant correlation could be established (r = 0.51, p = 0.01, N = 24). The results support the hypothesis that IGF-I plays a causal role in the initial renal hypertrophy of experimental diabetes.

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Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function

Annual Review of Physiology ◽

10.1146/annurev-physiol-031620-095920 ◽

2020 ◽

Vol 83 (1) ◽

Author(s):

Volker Vallon ◽

Subodh Verma

Keyword(s):

Ketone Bodies ◽

Heart Function ◽

Oxygen Demand ◽

Sglt2 Inhibitors ◽

Annual Review ◽

Publication Date ◽

Protective Mechanisms ◽

Filtration Barrier ◽

Urinary Glucose ◽

Resistance To Diuretics

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Rates of ketone-body formation in the perfused rat liver

Biochemical Journal ◽

10.1042/bj1120595 ◽

1969 ◽

Vol 112 (5) ◽

pp. 595-600 ◽

Cited By ~ 59

Author(s):

H. A. Krebs ◽

Patricia G. Wallace ◽

R. Hems ◽

R. A. Freedland

Keyword(s):

Fatty Acids ◽

Rat Liver ◽

Ketone Bodies ◽

Short Chain Fatty Acids ◽

Diabetic Rats ◽

Isolated Perfused Rat Liver ◽

Perfused Liver ◽

Perfused Rat Liver ◽

Normal Range ◽

Physiological Value

1. The rates of formation of acetoacetate and β-hydroxybutyrate by the isolated perfused rat liver were measured under various conditions. 2. The rates found after addition of butyrate, octanoate, oleate and linoleate were about 100μmoles/hr./g. wet wt. in the liver of starved rats. These rates are much higher than those found with rat liver slices. 3. The differences between the rates given by slices and by the perfused organ were much higher with the long-chain than with short-chain fatty acids. The increments caused by oleate and linoleate were 12 and 16 times as large in the perfused organ as in the slices, whereas the increments caused by butyrate and octanoate were about four times as large. 4. The rates of ketogenesis in the unsupplemented perfused liver of well-fed rats, and the increments caused by the addition of fatty acids, were about half of those in the liver from starved rats. 5. The value of the [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was raised by octanoate, oleate and linoleate. 6. Carnitine did not significantly accelerate ketogenesis from fatty acids. 7. Oleate formed up to 82% of the expected yield of ketone bodies. 8. In the liver of alloxan-diabetic rats the endogenous rates of ketogenesis were raised, in some cases as high as in the liver from starved rats, after addition of oleate. 9. On addition of either β-hydroxybutyrate or acetoacetate to the perfusion medium the liver gradually adjusted the [β-hydroxybutyrate]/[acetoacetate] ratio towards the normal range. 10. The [β-hydroxybutyrate]/[acetoacetate] ratio of the medium was about 0·4 when slices were incubated, but near the physiological value of 2 when the liver was perfused. 11. The experiments demonstrate that for the study of ketogenesis slices are in many ways grossly inferior to the perfused liver.

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Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats

Biochemical Journal ◽

10.1042/bj2490565 ◽

1988 ◽

Vol 249 (2) ◽

pp. 565-572 ◽

Cited By ~ 18

Author(s):

M S M Ardawi

Keyword(s):

Small Intestine ◽

Ketone Body ◽

Ketone Bodies ◽

Diabetic Rats ◽

Glutamine Metabolism ◽

Gut Mucosa ◽

Streptozotocin Induced Diabetes ◽

Streptozotocin Diabetic Rats ◽

Short And Long Term

1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone-body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats.

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