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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triiodo-L-thyronine (T(3)) added in vitro to fat pads from normal, or propylthiouracil-treated rats enhanced the rate of release of glycerol and free fatty acids (FFA) in the presence of epinephrine. An effect of T(3) was also demonstrated in the presence of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, or glucagon in studies with tissue from normal rats. The minimal effective concentration of T(3) was approximately 2.5 x 10(-5) mole/liter for intact fat pads and 3 x 10(-6) mole/liter for fat cells. With fat pads from propylthiouracil-treated rats the effect of T(3) was not apparent until the 3rd hr of incubation. Enhancement of epinephrine-stimulated lipolysis by T(3) was evident during the 1st hr of incubation of fat pads from normal rats, and fat cells responded almost immediately to the presence of T(3). When added alone or in the presence of theophylline, 3',5'-adenosine monophosphate or its dibutyryl derivative, T(3) had little or no effect on lipolysis. The effect of T(3) was observed with or without glucose in the medium, and was not inhibited by cycloheximide or actinomycin D. It did not persist when tissues, after incubation in the presence of T(3) were transferred to medium without T(3). No effect of T(3) on glucose uptake in the presence of epinephrine, ACTH, or insulin was demonstrated.
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PMID:An in vitro effect of triiodothyronine on rat adipose tissue. 429 92

1. A method for measuring the lipogenesis from [(14)C]glucose by single fat cells is described: (i) after incubation with ;carrier-free' [U-(14)C]glucose (0.55 mu-mole/ml.), collagenase-isolated fat cells were fixed with osmium tetroxide; (ii) similarly incubated pieces of epididymal fat pads were treated with osmium tetroxide for 90 sec, whereby only the superficial cells are fixed, and the tissue was then disintegrated by shaking with collagenase. The osmium-fixed free cells were washed, sucked into a micropipette, measured under a microscope and assayed individually for (14)C-activity.2. There was a quantitative recovery of (14)C-lipid activity from osmium-fixed single cells.3. Both collagenase-isolated cells and in situ fixed surface cells were normally distributed with respect to diameters (for both cell groups from ad lib. fed rats of ca. 110 g; mean diameter, about 55 mum; S.D. about 7 mum).4. Frequency distribution curves (number of fat cells versus (14)C-lipogenesis per cell) were asymmetric and very broad (coefficient of variation about 50%) for collagenase-isolated cells incubated with insulin (10(3) mu-u./ml.). Frequency distribution curves for surface cells obtained from similarly incubated pieces of epididymal fat pads showed a coefficient of variation of the same magnitude, whereas the mean lipogenesis of these cells was only about one third of that of the isolated cells.5. Collagenase-isolated cells incubated in the presence of insulin (10(3) mu-u./ml.) showed a weak but highly significant positive correlation between fat cell diameter and (14)C-lipogenesis (eight rats, r about 0.5 and P < 0.001 for each rat). Analysis of the relationship: lipogenesis = k x diameter to the exponent of beta showed that the estimates of beta varied significantly from rat to rat (range: 1.3-2.9). Similar correlations between cell size and lipogenesis were found both for cells incubated with insulin in various submaximal concentrations and for cells incubated without insulin.6. Small and large cells from the same rat were equally sensitive to insulin.7. Statistical analysis of frequency distribution curves (number of cells versus (14)C-lipogenesis per unit surface area) representing cells from the same rat incubated with insulin 0, 2.5, 5, 10, and 10(3) mu-u./ml., respectively, suggests that insulin exerts a graded influence on the lipogenesis of each fat cell.
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PMID:Lipogenesis and insulin sensitivity of single fat cells. 436 2

The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/ml. In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P=<0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production. It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.
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PMID:Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. 480 35

1. Thin diaphragm muscles in dialysed serum maintained their total sodium at values similar to those found in vivo. The fibre sodium exchanged with a half-time of 5 min, and the flux was 10 p-mole.cm(-2).sec(-1). The internal sodium was less than 10 mumoles/g fibre water and the ratio of external to internal sodium was at least 15. The calculated energy expenditure for sodium extrusion was less than 2% of the resting metabolism.2. In physiological saline the half-time for exchange of fibre sodium was similar to that in serum, but in saline there was an increase in sodium permeability and a raised total and fibre sodium.3. Muscles treated with insulin (0.02 u./ml.) showed a more rapid exchange of sodium compared with muscles in saline, with no change in the permeability to sodium. Insulin also affected sodium movements in the absence of external glucose.4. In saline the fraction of sodium which exchanged rapidly occupied 0.33 by volume of the muscle, after corrections for diffusion, and this value was similar to the mannitol space.5. Fibre diameters were measured in frozen sections. Muscles prepared by fixation and embedding showed marked shrinkage.
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PMID:Sodium fluxes in diaphragm muscle and the effects of insulin and serum proteins. 571 45

1. The effect of somatostatin on the responses to moderate insulin hypoglycaemia and to 2-deoxyglucose has been examined in 2--3 week-old calves with cut splanchnic nerves. 2. Intravenous infusions of somatostatin (150 p-mole . kg-1 . min-1) completely suppressed release of glucagon, pancreatic polypeptide (PP) and insulin from the pancreas in response to 2-deoxyglucose (1.1 m-mole/kg I.V.). 3. The same dose of somatostatin completely blocked the rise in plasma PP concentration that normally occurs in response to moderate insulin hypoglycaemia and significantly delayed the rise in plasma pancreatic glucagon concentration. The hypoglycaemic response to insulin was also found to be intensified by the administration of somatostatin. 4. It is concluded that each of the pancreatic neuroendocrine responses, that are now known to be mediated via the parasympathetic innervation, is suppressed in the presence of somatostatin in the young calf.
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PMID:The effect of somatostatin on pancreatic endocrine responses mediated via the parasympathetic innervation in the conscious calf. 611 66

We describe a method for covalent binding of insulin to the outer surface of multilamellar liposomes loaded with spin label. Encapsulation of the label Tempocholine-nitroxide within the aqueous phases of liposomes is controlled by Electron Spin Resonance. The binding of insulin is performed using the Carlsson's heterobifunctional reagent: N-succinimidyl 3-(2-pyridyldithio) propionate. The coupling method results in efficient attachment of 2. 64.10(-4) mole of insulin per mole of phospholipid; the integrity of these vesicles is not modified as confirmed by spin resonance analysis. Moreover, the liposome-coupled insulin retains its antigenic specificity as shown by radioimmunoassays.
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PMID:Covalent attachment of insulin to the outer surface of liposomes. 619 74

125I-labeled insulin has been cross-linked to alpha 2-macroglobulin (alpha 2M) via a disulfide bond. The resulting insulin-alpha 2M conjugate carried 2.2 insulin moieties per mole of alpha 2M and was able to deliver insulin into rat hepatoma cells H35 and HTC. The insulin delivery was mediated predominantly through alpha 2M receptors and 2 h after binding it was found in the lyposomal fractions in the form of conjugate. When the conjugate was applied to rat hepatoma cells it stimulated activity of tyrosine aminotransferase (TAT) with a potency one-half that of native insulin. Hepatoma cells which were treated with conjugate in the presence of bacitracin were also stimulated for TAT activity. Since bacitracin completely inhibited the alpha 2M binding to its receptors, but inhibited conjugate binding by only 80%, this stimulation must have resulted from the remaining binding of conjugate. These results indicate that the insulin-alpha 2M conjugate was biologically active if it bound to insulin receptors, but that the conjugate bound and internalized through alpha 2M receptors did not act as a mediator for TAT activation. Our results using Percoll density gradients indicate a difference in intracellular processing between insulin, alpha 2M and the conjugate. Mechanisms of action of the conjugate are discussed in relation to the receptor-mediated endocytic pathways.
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PMID:Transmembrane delivery of polypeptide hormones bypassing the intrinsic cell surface receptors: a conjugate of insulin with alpha 2-macroglobulin (alpha 2M) recognizing both insulin and alpha 2M receptors and its biological activity in relation to endocytic pathways. 620 13

Phosphorylation site stoichiometries were determined for skeletal muscle glycogen synthase purified from control, alloxan-diabetic, and epinephrine-treated rabbits. One method of analysis was direct determination of the total in vivo phosphate content of each site after reverse phase high performance liquid chromatography separation of a complete tryptic digest of the purified synthase. The second method of analysis, in vitro phosphorylation, was based on the premise that in vitro 32P incorporation into each site would be inversely related to the in vivo phosphate content of that site. Glycogen synthase from control rabbits had the following distribution of in vivo phosphate (mole of phosphate/mol of site): site 1a, 0.29 +/- 0.08; site 5, 0.62 +/- 0.07; site 3, 0.46 +/- 0.06; site 1b, 0.23 +/- 0.03; and site 2, 0.43 +/- 0.07. Synthase from diabetic rabbits had 2-fold elevations of in vivo phosphate contents of sites 2 and 3. Epinephrine resulted in increased phosphorylation in vivo of site 1b (2.0-fold), site 2 (2.0-fold), and site 3 (1.5-fold). The in vitro phosphorylation analysis showed decreased 32P incorporation in vitro (indicative of increased in vivo phosphorylation) as follows: epinephrine, site 1a, site 3, site 1b, site 2; diabetic, site 3, site 2. The effect of diabetes on the in vitro phosphorylation of sites 2 and 3 was reversed by insulin treatment. We conclude that the major effect of epinephrine, phosphorylation of sites 1a, 1b, and 2, is mediated by the activation of the cAMP-dependent kinase. The mechanisms accounting for the phosphorylation of site 3 in response to epinephrine and phosphorylation of sites 2 and 3 in the diabetic state are under investigation.
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PMID:Effects of epinephrine, diabetes, and insulin on rabbit skeletal muscle glycogen synthase. Phosphorylation site occupancies. 632 4

Evaluation of insulin sensitivity in 12 patients with myotonic dystrophy gave results different from those found in other insulin-resistant conditions. Nine of our subjects were insensitive to exogenous insulin, but only three had elevated fasting insulin concentrations. Eight had an excessive insulin response to a glucose challenge. Monocyte insulin receptor affinity was decreased (myotonics, 1.21 +/- 0.74 X 10(9) liters per mole; controls, 2.62 +/- 1.28 X 10(9)), and this parameter correlated best with the insulin resistance. No circulating receptor antibody or insulin binding inhibitor was found. Our studies suggest that the insulin resistance seen in patients with myotonic dystrophy is related to decreased insulin receptor affinity.
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PMID:Insulin resistance in patients with myotonic dystrophy. 634 79

The marked propensity of insulin to self-associate into large aggregates causes significant mechanical problems in insulin delivery devices and may also stimulate production of a tissue-amyloid A precursor in some patients. Although conventionally prepared sulfated insulin (SI) resists aggregation, clinical application has been limited by major insulin bioactivity losses that occur during synthesis. To eliminate this problem, insulin sulfation was carried out in the organic solvent dimethylformamide in the presence of condensing agents such as N,N'-dicyclohexyl carbodiimide (DCC) and a sulfate donor. With this new procedure, the degree of sulfation could be controlled over an eightfold range by varying the amount of condensing agent. The bioactivity of these new SI derivatives varied between 78% and 87% of unmodified insulin. Insulin aggregation, induced by passage through a syringe and needle, did not occur with derivatives having two or more sulfate moieties per insulin molecule. Diffusion velocity studies using "non-aggregated" insulin solutions demonstrated that aggregates were present in crystalline zinc and sodium porcine insulin. In contrast, SI having more than 0.5 mole sulfate per mole of insulin dialyzed as it were predominantly in the monomeric form. Results from the studies described in this report now provide the means for selectively designing and preparing specific high-potency, non-aggregating insulins, which may be necessary for optimal use of current and future insulin delivery devices.
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PMID:Preparation of high-potency, non-aggregating insulins using a novel sulfation procedure. 636 Jul 57


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