The effect of anti-insulin serum and alloxan-diabetes on the distribution and multiple forms of hexokinase in lactating rat mammary gland

1. The distribution and multiple forms of hexokinase activity in lactating rat mammary gland were investigated in alloxan-diabetic rats and in rats treated with anti-insulin serum. It was found that 46% of the total hexokinase of mammary-gland tissue from control rats was in the particulate fraction, but this percentage was decreased in the alloxan-diabetic rats to 11% of the total hexokinase. The hexokinase activity of the soluble fraction was not significantly altered but there was a decrease in the type II/type I quotient. 2. The early changes that occurred on insulin deprivation were studied 1hr. after administration of anti-insulin serum to lactating rats, at which time the hexokinase bound to the particulate fraction had decreased to 11% of the control value and that in the soluble fraction had increased by approx. 50%. The hexokinase type II/type I quotient in the soluble fraction was significantly decreased. These results suggested that there was a release of particulate-bound hexokinase in rats treated with anti-insulin serum.

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Effect of alloxan-diabetes on multiple forms of hexokinase in adipose tissue and lung

Biochemical Journal ◽

10.1042/bj1051301 ◽

1967 ◽

Vol 105 (3) ◽

pp. 1301-1305 ◽

Cited By ~ 14

Author(s):

Patricia McLean ◽

J. Brown ◽

Eileen Walters ◽

K. Greenslade

Keyword(s):

Adipose Tissue ◽

Gel Electrophoresis ◽

Alloxan Diabetes ◽

Diabetic Rats ◽

Type I ◽

Starch Gel Electrophoresis ◽

Type Ii ◽

Multiple Forms ◽

Starch Gel ◽

Hexokinase Type I

Comparison has been made of the effect of alloxan-diabetes on the multiple forms of hexokinase (EC 2.7.1.1) in adipose tissue and lung. Types I and II hexokinase were distinguished in adipose tissue by their different stabilities to heat treatment, which made it possible to determine the activity of each form spectrophotometrically; additional confirmatory evidence was obtained from starch-gel electrophoresis. Type II hexokinase was markedly depressed in adipose tissue from alloxan-diabetic rats. Lung contained types I, II and III hexokinase, type I predominating. There was no significant change in the pattern of these multiple forms of hexokinase in lung from alloxan-diabetic rats. These results are discussed in relation to current ideas that the insulin-sensitivity of a tissue may be correlated with the content of type II hexokinase.

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Moderate Beer Consumption Modifies Tumoral Growth Parameters and Pyrrolidone Carboxypeptidase Type-I and Type-II Specific Activities in the Hypothalamus-Pituitary-Mammary Gland Axis in an Animal Model of Breast Cancer

Nutrition and Cancer ◽

10.1080/01635581.2020.1856891 ◽

2020 ◽

pp. 1-13

Author(s):

María Jesús Ramirez-Expósito ◽

José Manuel Martínez-Martos ◽

Vanesa Cantón-Habas ◽

María del Pilar Carrera-González

Keyword(s):

Breast Cancer ◽

Animal Model ◽

Mammary Gland ◽

Growth Parameters ◽

Type I ◽

Type Ii ◽

Beer Consumption ◽

Specific Activities

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Nutritional and hormonal regulation of malic enzyme synthesis in rat mammary gland

Biochemical Journal ◽

10.1042/bj2360441 ◽

1986 ◽

Vol 236 (2) ◽

pp. 441-445 ◽

Cited By ~ 4

Author(s):

M F Lobato ◽

M Ros ◽

F J Moreno ◽

J P García-Ruíz

Keyword(s):

Enzyme Activity ◽

Mammary Gland ◽

Malic Enzyme ◽

Hormonal Regulation ◽

Relative Rate ◽

Enzyme Synthesis ◽

Soluble Proteins ◽

Control Value ◽

Rat Mammary Gland ◽

Malic Enzyme Activity

Cytosolic malic enzyme was purified from rat mammary gland by L-malate affinity chromatography. The pure enzyme obtained was used to produce a specific antiserum in a rabbit. Relative synthesis of malic enzyme in the mammary gland of mid-lactating rats was 0.097%, measured by labelling the enzyme in isolated acini. When food was removed, malic enzyme synthesis decreased to 35% and 20% of the control value at 4 and 6 h respectively. Incorporation of [3H]leucine into soluble proteins was constant during the first 6 h of starvation. When lactating rats (maintained with their pups) were starved for 24 h and then re-fed, the relative rate of enzyme synthesis increased 2.5-, 4-, and 4.5-fold at 3 h, 6 h and 18 h respectively after initiation of re-feeding. The relative rate of malic enzyme synthesis was about 50% of normal at 15 h after weaning, whereas the rate of synthesis of soluble proteins did not change. Administration of bromocriptine or adrenalectomy of lactating rats decreased the relative rate of synthesis of malic enzyme by 40% or 30% respectively; these effects were counteracted by hormone supplementation. Hormone therapy also caused an increase in the rate of incorporation of [3H]leucine into soluble proteins and in malic enzyme activity.

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Tetracyclines Inhibit Protein Glycation in Experimental Diabetes

Advances in Dental Research ◽

10.1177/08959374980120011201 ◽

1998 ◽

Vol 12 (1) ◽

pp. 152-158 ◽

Cited By ~ 15

Author(s):

M.E. Ryan ◽

N.S. Ramamurthy ◽

L.M. Golub

Keyword(s):

Diabetic Rats ◽

Protein Glycation ◽

Type I ◽

Type Ii ◽

Tissue Samples ◽

Glycated Proteins ◽

Uncontrolled Diabetes ◽

Skin Collagen ◽

Micro Organisms

Glycation of proteins, which is accelerated in the diabetic state, has been implicated in many of the long-term complications of diabetes. This process can be inhibited by members of the tetracycline family of compounds. This novel finding is supported by studies conducted on drug (streptozotocin)induced Type I and genetic (ZDF/Gmi- fa/fa) Type II diabetic rats. These animals were orally gavaged daily with 5 mg of doxycycline and a variety of non-antimicrobial chemically modified tetracycline derivatives for time periods of 3 weeks to 11 months, while control untreated diabetic and nondiabetic animals were gavaged with vehicle alone (2% CMC). Blood and tissue samples were collected and analyzed for glucose and glycated proteins. None of the treatments had any effect on the severity of hyperglycemia or the intracellular glycation of hemoglobin of either Type I or II diabetic animals. However, the tetracycline analogues did affect the extracellular glycation of several proteins such as those found in the serum as well as skin collagen. In the Type II (ZDF) animals, initial mortality (3-5 months) was seen only in the doxycycline-treated animals, associated with infection by tetracycline-resistant micro-organisms, which was eventually surpassed by mortality rates in the untreated diabetics (6-9 months). CMT treatment not only decreased mortality but also increased longevity in the Type II diabetic animals, most likely by preventing the development of a number of long-term complications of uncontrolled diabetes, including glycation of proteins, that eventually lead to the demise of untreated diabetic animals.

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Characterization of the protein kinase activities of human platelet supernatant and particulate fractions

Biochemical Journal ◽

10.1042/bj2180285 ◽

1984 ◽

Vol 218 (2) ◽

pp. 285-294 ◽

Cited By ~ 10

Author(s):

S E Salama ◽

R J Haslam

Keyword(s):

Protein Kinase ◽

Cyclic Amp ◽

Soluble Fraction ◽

Deae Cellulose ◽

Type I ◽

Type Ii ◽

Dependent Protein Kinase ◽

Regulatory Subunits ◽

Dependent Protein ◽

Triton X

After human platelets were lysed by freezing and thawing in the presence of EDTA, about 35% of the total cyclic AMP-dependent protein kinase activity was specifically associated with the particulate fraction. In contrast, Ca2+-activated phospholipid-dependent protein kinase was found exclusively in the soluble fraction. Photoaffinity labelling of the regulatory subunits of cyclic AMP-dependent protein kinase with 8-azido-cyclic [32P]AMP indicated that platelet lysate contained a 4-fold excess of 49 000-Da RI subunits over 55 000-Da RII subunits. The RI and RII subunits were found almost entirely in the particulate and soluble fractions respectively. Chromatography of the soluble fraction on DEAE-cellulose demonstrated a single peak of cyclic AMP-dependent activity with the elution characteristics and regulatory subunits characteristic of the type-II enzyme. A major enzyme peak containing Ca2+-activated phospholipid-dependent protein kinase was eluted before the type-II enzyme, but no type-I cyclic AMP-dependent activity was normally observed in the soluble fraction. The particulate cyclic AMP-dependent protein kinase and associated RI subunits were solubilized by buffers containing 0.1 or 0.5% (w/v) Triton X-100, but not by extraction with 0.5 M-NaCl, indicating that this enzyme is firmly membrane-bound, either as an integral membrane protein or via an anchor protein. DEAE-cellulose chromatography of the Triton X-100 extracts demonstrated the presence of both type-I cyclic AMP-dependent holoenzyme and free RI subunits. These results show that platelets contain three main protein kinase activities detectable with histone substrates, namely a membrane-bound type-I cyclic AMP-dependent enzyme, a soluble type-II cyclic AMP-dependent enzyme and Ca2+-activated phospholipid-dependent protein kinase, which was soluble in lysates containing EDTA.

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The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver

Biochemical Journal ◽

10.1042/bj1110713 ◽

1969 ◽

Vol 111 (5) ◽

pp. 713-725 ◽

Cited By ~ 38

Author(s):

F. Novello ◽

J. A. Gumaa ◽

Patricia McLean

Keyword(s):

Diabetic Rats ◽

Pentose Phosphate ◽

Hexokinase Activity ◽

Transketolase Activity ◽

Control Value ◽

Phosphogluconate Dehydrogenase ◽

Pentose Phosphate Cycle ◽

Oxidative Reactions ◽

Glucose 6 Phosphate Dehydrogenase ◽

Adrenalectomized Rats

1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ‘overshoot’ effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30–40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine–zinc–insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine–zinc–insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.

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T1810 Hepatic Electrical Stimulation Reduces Blood Glucose in Both Type-I and Type-II Diabetic Rats

Gastroenterology ◽

10.1016/s0016-5085(09)62691-3 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-584-A-585 ◽

Cited By ~ 1

Author(s):

Jie Chen ◽

Jieyun Yin ◽

Lin Lin ◽

Pankaj J. Pasricha ◽

Jiande Chen

Keyword(s):

Electrical Stimulation ◽

Blood Glucose ◽

Diabetic Rats ◽

Type I ◽

Type Ii

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Effects of Type II diabetes on capillary hemodynamics in skeletal muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00290.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. H2439-H2444 ◽

Cited By ~ 82

Author(s):

Danielle J. Padilla ◽

Paul McDonough ◽

Brad J. Behnke ◽

Yutaka Kano ◽

K. Sue Hageman ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Glucose ◽

Type Ii Diabetes ◽

Capillary Tube ◽

Diabetic Rats ◽

Diabetic Rat ◽

Diabetic Patients ◽

Type I ◽

Type Ii ◽

Gk Rats

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dc was not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2 delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2 delivery and diffusive O2 transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2 exchange characteristic of Type II diabetic patients.

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