[quote]Christian Thibaudeau wrote:
retailboy wrote:
Thibs,
The one scientific theory behind this new pre-workout nutrition you have presented has been that catecholamines blunt the effects of insulin - correct me if I’m wrong please.
My 7+ years of formal education in the biology/clinical sector has taught me no such direct pathway. I have actually been taught that with increase catecholamines your muscles increase the uptake of glucose which improves the effects of insulin.
Since it seems T-Nation’s next big supplement and your new pre/intra/post workout nutrition protocol seem to hinge greatly on the evidence behind them - I was hoping you had ANY type of scientific backing for either instead of just anecdotal (I understand that science is behind in this area of research but still there should be research that supports some of the basics of your protocol - even if it is as simple as by what pathway the catecholamines blunt insulin).
Side note: I have been getting better results over the past two years since I’ve switched to ‘high’ pre and intra carbohydrate intake from the typical post-workout protocol.
Thank you for your time Thibs!
David
Well, since you have been witnessing the powerful effects yourself, why the need for a study?
http://www.springerlink.com/content/j76485v703822g23/
Also…
J Clin Invest. 1976 March; 57(3): 791â??795.
doi: 10.1172/JCI108338.
PMCID: PMC436715
Copyright notice
A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus.
R P Robertson, J B Halter, and D Porte, Jr
This article has been cited by other articles in PMC.
Abstract
To determine whether endogenous alpha-adrenergic activity contributes to abnormal insulin secretion in nonketotic, hyperglycemic, diabetic patients, alpha-adrenergic blockade was produced in normal and diabetic subjects. The diabetics had a significantly (P less than 0.01) greater increase in circulating insulin 1 h after an intravenous phentolamine infusion than did the normal subjects. During the phentolamine infusion, there was also a significant augmentation of acute insulin responses to intravenous glucose (20 g) pulses in normal subjects (P less than 0.05) and diabetics (P less than 0.02); this augmentation was fivefold greater in the diabetics. Simultaneous treatment with the beta-adrenergic blocking agent, propranolol, did not alter these findings. Thus a role for exaggerated endogenous alpha-adrenergic activity in abnormal insulin secretion of the diabetic subjects is suggested. To determine whether this alpha-adrenergic activity might be related to elevated circulating catecholamines, total plasma-catecholamine levels were compared in normal and nonketotic diabetic subjects given intravenous glucose pulses. These levels were significantly greater (P less than 0.02) in the diabetic compared to the normal group before the glucose pulse, and increased significantly in both groups (P less than 0.02 and less than 0.001, respectively) after the pulse. These data suggest that excessive catecholamine secretion may lead to an abnormal degree of endogenous alpha-adrenergic activity, which contributes to defective insulin secretion in diabetic subjects.
AND…
FEBS Lett. 1987 Jul 13;219(1):139-44.
Catecholamine inhibition of Ca2±induced insulin secretion from electrically permeabilised islets of Langerhans.
Jones PM, Fyles JM, Persaud SJ, Howell SL.
Noradrenaline (1-10 microM) inhibited Ca2±induced insulin secretion from electrically permeabilised islets of Langerhans with an efficacy similar to that for inhibition of glucose-induced insulin secretion from intact islets. The inhibition of insulin secretion from permeabilised islets was blocked by the alpha 2-adrenoreceptor antagonist, yohimbine. Adenosine 3’,5’-cyclic monophosphate (cAMP) did not relieve the noradrenaline inhibition of Ca2±induced secretion from the permeabilised islets, although noradrenaline did not affect the secretory responses to cAMP at substimulatory (50 nM) concentrations of Ca2+. These results suggest that catecholamines do not inhibit insulin secretion solely by reducing B-cell adenylate cyclase activity, and imply that one site of action of noradrenaline is at a late stage in the secretory process.
AND …
Biochem J. 1985 Mar 1;226(2):571-6.
Studies on the mechanism of inhibition of glucose-stimulated insulin secretion by noradrenaline in rat islets of Langerhans.
Morgan NG, Montague W.
Noradrenaline (norepinephrine) was shown to be a potent inhibitor of glucose-induced insulin release from rat pancreatic islets, with half-maximal inhibition of the secretory response to 20 mM-glucose occurring at approx. 0.3 microM, and complete suppression of the response occurring at 4 microM-noradrenaline. Inhibition of insulin secretion by noradrenaline was antagonized by the alpha 2-adrenergic antagonist yohimbine (half maximally effective dose approximately 1 microM), but was largely unaffected by the alpha 1-adrenergic antagonist prazosin at concentrations up to 50 microM, suggesting that the response was mediated by alpha 2-adrenergic receptors. Noradrenaline significantly reduced the extent of 45Ca2+ accumulation in glucose-stimulated islets, although as much as 5 microM-noradrenaline was required for 50% inhibition of this response. The ability of noradrenaline to inhibit islet-cell 45Ca2+ uptake was totally abolished in media containing 1 mM-dibutyryl cyclic AMP, suggesting that the response may have been secondary to lowering of islet cyclic AMP. Under these conditions, however, noradrenaline was still able to inhibit insulin secretion maximally. The data suggest that the site(s) at which noradrenaline acts to mediate inhibition of insulin secretion in rat islets lies distal to both islet-cell cyclic AMP accumulation and Ca2+ uptake
AND …
GTP-dependent inhibition of insulin secretion by epinephrine in permeabilized RINm5F cells. Lack of correlation between insulin secretion and cyclic AMP levels.
S Ullrich and C B Wollheim
Institut de Biochimie Clinique, Centre M�©dical Universitaire, Gen�¨ve, Switzerland.
Abstract
The mechanism by which alpha 2-adrenergic agonists inhibit exocytosis was investigated in electrically permeabilized insulin secreting RINm5F cells. In this preparation alpha 2-adrenoceptors remain coupled to adenylate cyclase, since basal- and forskolin-stimulated cyclic AMP production was lowered by epinephrine and clonidine by 30-50%. Cyclic AMP levels did not correlate with the rate of insulin secretion. Thus, at low Ca2+, forskolin enhanced cyclic AMP levels 5-fold without eliciting secretion, and Ca2±stimulated secretion was associated with decreased cyclic AMP accumulation. Epinephrine (plus propranolol) inhibited Ca2±induced insulin secretion in a GTP-dependent manner. The maximal inhibition (43%) occurred at 500 microM GTP. Clonidine also inhibited Ca2±stimulated secretion. Replacement of GTP by GDP or by the nonhydrolyzable GTP analog guanosine 5’-(3-O-thio)triphosphate as well as treatment of the cells with pertussis toxin prior to permeabilization abolished epinephrine inhibition of insulin secretion. Pertussis toxin did not affect Ca2±stimulated secretion. Insulin release stimulated by 1,2-didecanoyl glycerol was also lowered by epinephrine suggesting an effect distal to the activation of protein kinase C (Ca2+/phospholipid-dependent enzyme). These results taken together with the ability of epinephrine to inhibit ionomycin-induced insulin secretion in intact cells suggest that alpha 2-adrenergic inhibition is distal to the generation of second messengers. A model is proposed for alpha 2-adrenoceptor coupling to two effector systems, namely the adenylate cyclase and the exocytotic site in insulin-secreting cells.
AND …
i: 10.1172/JCI107887.
PMCID: PMC301695
Copyright notice
Glucagon Secretion from the Perfused Rat Pancreas STUDIES WITH GLUCOSE AND CATECHOLAMINES
Gordon C. Weir, Stephen D. Knowlton, and Donald B. Martin
Diabetes Unit and Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114
Diabetes Unit Harvard Medical School, Boston, Massachusetts 02114
This article has been cited by other articles in PMC.
Abstract
The isolated in situ perfused rat pancreas was used to study glucose and catecholamine control of glucagon secretion, and to investigate the possible role of endogenous cyclic AMP as a mediator of this secretory process. When perfusate glucose was acutely dropped from 100 to 25 mg/100 ml, glucagon was released in a biphasic pattern with an early spike and a later plateau-like response. 300 mg/100 ml glucose suppressed glucagon secretion to near the detection limit of the radioimmunoassay (15 pg/ml). When perfusate glucose was dropped from 300 to 25 mg/100 ml, a delayed, relatively small peak occurred suggesting persisting alpha cell suppression by prior high glucose exposure. 2-Deoxy d-glucose stimulated glucagon secretion and inhibited insulin secretion.
Glucagon was secreted in a biphasic pattern in response to both 2.7 Ã?? 10-7 M epinephrine and norepinephrine. The glucagon response to epinephrine was markedly suppressed by glucose at 300 mg/100 ml, and the biphasic response pattern was obliterated. Glucose evoked a two-phase insulin secretory pattern, and the second phase was markedly and rapidly inhibited by epinephrine. Pancreases were perfused with glucose at 300 mg/100 ml which was then lowered to 80 mg/100 ml. 5 min later, epinephrine was infused and definite blunting of the first-phase spike occurred. 10 mM theophylline produced modest rapid uniphasic stimulation of glucagon release, and, in addition, caused enhancement of epinephrine-stimulated glucagon release. An inhibitory influence upon epinephrine-stimulated glucagon was observed as well. Insulin secretion was stimulated by 10 mM theophylline, and this stimulation was inhibited by epinephrine.
You get the point…[/quote]
Man am I glad that smarter guys than me are working on this. I mean I get the point, but I would have had a hell of a time creating a protocol around this information.