The figure shows the skin projection areas of all neuronal central for Realising Factors, including GH-RF.
I’d like to emphasize a new, clinical, quantum-biophysical-semeiotics, refined, reliable method, rapid to apply, and really efficacious in selecting since birth individuals affected by impaired glucose metabolism, not dependent of its seriousness; I termed it Endogenous Gucagon Test.
Truly, I’ve already described a lot of other methods, which proved to be useful in a long clinical experience (See former article on this topic in my website www.semeioticabiofisica.it).For instance, in health, Apnoea Test, lasting 5 seconds, does not brings about parameter values of glucose blood level, bedside evaluated with the original semeiotics (1-8), indicating that both insulin and glucagon secretion is in normal range.
On the contrary, in individuals, apparently healthy, but involved by Diabetic “and” Dislipidemic Constitution, with diabetic INHERITED Real Risk (6-8), such as manoeuvre causes significant alteration of parameters values, showing an impairment in both secretions. Exclusively in the later case, during apnoe test, liver microcirculatory bed shows the secretion phase after 11 sec latency time: after interrupting physiological oscillations, liver low margin lowers significantly and quickly for about
Analogously, in heath, “mild-intense” digital pressure upon skin projection area of GH-RF (2), brings about pancreas decongestion, lasting 8 sec. exactly (= highly reduced insulin secretion), followed at 9 sec. by pancreas rapid and significant enlargement (= glucagon secretion).
Interestingly, at 11 sec. precisely, liver size augments quickly, showing above-referred secretion phase of its microcirculation, according to my Angiobiopathy theory (2-4).
On the contrary, in case of IGT or overt diabetes, under the same experimental condition, the glucose secretion phase of liver hepatic enlargement, detected with auscultatory percussion, appears after a reduced latency time, i.e., less than 11 sec., e.g., 10-8 sec. and respectively 7-6 sec. or less, while the duration of pancreatic decongestion persists for a shortest time, in relation to the severity of underlying glucose metabolism disorder.
We must agree with the statement that Diabetes is a serious growing epidemics! However, I’d like to state that with the aid of Quantum Biophysical Semeiotics, I've discovered the until now unknown, newborn-pathological, subtype a) oncological, and b), aspecific, type I, Endoarteriolar Blocking Devices in tissue, wherein does really exist the real risk of human common and severe diseases, as diabetes. Obviously that happens in individuals with defined Biophysical Semeiotics Constitutions, in our case, Diabetic “and” Dyslipidemic (Bibliography in my above-cited website) (1-6). Interestingly, e.g., in Diabetes Primary Prevention (PP), we need new clinical tools, aiming to lower the increasing number of patients, although the present, expensive screening: http://www.semeioticabiofisica.it, Practical Applications: Diabetes, and Biophysical-Semeiotic Constitutions (1-7).
For instance, in the normal Langheran’s islets microcirculatory bed, there are exclusively “normal” type II (= in arterioles, according to Hammersen), but not type I (= in small arterioles) endoarteriolar blocking devices, i.e. EBD, of first and second classes, according to S.B. Curri (See http://www.semeioticabiofisica.it/microangiologia).
In health, i.e., individual not involved by Diabetic Constitution, we cannot observe type I, newborn-pathological, EBD in above-mentioned biological system.
On the contrary, in subjects affected by diabetic constitution as well as diabetic "Inherited Real Risk" and overt diabetes, of course, we observe, with the aid of Quantum Biophysical Semeiotics, also type I, newborn-pathological, subtype b) aspecific, EBD, facilitating the diagnosis and consequently diabetes primary prevention. In addition, the evaluation of Insulin Secretion Acute Pick Renal Test is significantly impaired, corroborating the clinical diagnosis (1-3) (See above cited- website, Practical Applications, and Glossary).
Finally, an interesting clinical tool in recognizing diabetic constitution-dependent inherited real risk, as well as in diagnosing diabetes since early stages and diabetic monitoring proved to be bedside Biophysical-Semeiotic Osteocalcin Test (10). As a matter of fact, Pre-hypertension during Young Adulthood may be involved by Coronary Calcium Later in Life exclusively in presence of Inherited Real Risk of CAD, typical for individuals with lithyasic Constitution, present in about 50% of all cases of Pre-Metabolic and Metabolic Syndrome (www.semeioticabiofisica.it; Constitutions and Bibliography) (36).
Considering the frequent association between hypertension and diabetes, more important, in my opinion based on 53-year-long clinical experience, is bedside recognizing diabetic predisposition, now-a-days possible since birth, utilising a lot of methods, different in difficulty, but all reliable. For the first time, from the clinical view-point, I have recently illustrated an original manoeuvre, based on a singular activity of osteocalcin, and reliable in bedside detecting diabetes in one minute, with the aid of a stethoscope (10). In fact, osteocalcin, a product of osteoblasts, among other action mechanisms, stimulates both insulin secretion and insulin receptor sensitivity. As a consequence, osteocalcin, secreted by above-mentioned bone cells during mean-intense lasting digital pressure – for instance – applied upon lumbar vertebrae, brings about increasing pancreatic diameters, i.e., technically speaking, type I, associated, Langherans’s islet microcirculatory activation, so that doctors assess pancreas size augmentation, which in health, lasts 10 seconds exactly (1-11). After that, pancreas diameters return to basal value for 3 sec. The second pancreas size increasing lasts 20 sec., and finally the third show the highest value: 30 sec. I terme such as clinical investigation. On the contrary, in case of diabetic constitution (3, 4, 11) the first pancreas increasing persists normally (10 sec.), but both the second and the third are less than physiological ones (i.e., less than 20 sec. and respectively 30 sec.). In presence of intense inherited real risk of diabetes (6), such impairment is greater. Finally, in case of diabetes the alteration is present already in the first evaluation, wherein duration appears less than 10 sec., inversely related with disorder seriousness. Subsequently, I have ascertained that Ronald’s Manoeuvre result pathological already in individuals involved by both Diabetic Constitution and Inherited Diabetic Real Risk (1-11). Interestingly, not only in examining subject, but also in all others, even if kilometres way from him (her), according to Lory’s experiment, based of no local realm in biological systems (12), pancreas show identical modifications, allowing doctors to made clinical diagnosis until now impossible (1-12).
Insulin and Glucagon in diabetes pathogenesis.
Glucagon plays notoriously an important role in glucose homeostasis by regulating hepatic glucose output in both normo- and hypoglycemic conditions, as I have demonstrated for the first time clinically (1-6, 14, 15). Recently authors referred that adult male Insulin Receptors Knock Out mice exhibited mild glucose intolerance, hyperglycemia, and hyperglucagonemia in the fed state and enhanced glucagon secretion in response to L-arginine stimulation (16). Hyperinsulinemic-hypoglycemic clamp studies revealed an enhanced glucagon secretory response and an abnormal norepinephrine response to hypoglycemia in -IRKO mice (16). Glucagon, secreted from the pancreatic -cells, counters the actions of insulin and corrects hypoglycemia by enhancing hepatic glucose output and gluconeogenesis (17,18). Inappropriate glucagon secretion is often observed in patients with diabetes, as I demonstrated at the bedside with quantum-biophysical-semeiotics (see later on), and a defective glucagon response to hypoglycemia in hyperinsulinemic states frequently exacerbates hypoglycemic attacks and limits intensive insulin therapy (19, 20). On the other hand, excess glucagon secretion (21) and increase in -cells in pancreatic islets in type 1 and type 2 diabetes have been reported to worsen the hyperglycemia (21, 22).
The regulation of glucagon secretion involves a complex interplay of signals, including glucose, intra-islet paracrine factors, and the central and autonomic nervous systems (23). Insulin, secreted from -cells, has been proposed as one of the intra-islet paracrine factors that can modulate the secretion of glucagon by neighboring -cells (24 , 25).
Endogenous Glucagon Test: patho-physiological mechanisms..
“Mean-intense” digital pressure, applied upon GH-RF neuronal centre skin projection area (Fig. 1) stimulates its secretion and subsequently that of hypophyseal GH, that in turns improves glucagon secretion by pancreatic islet alfa-cells, since GH lowers significantly insulin secretion (13) (Fig.1).
As above referred, such stimulation brings about interesting, characteristic modifications of pancreatic and then hepatic fluctuations. Really, the same events can be observed also if digital pressure is “intense”, lasting a second, due to quantum biophysics, as I have illustrated in details previously (26-35).
In heath, under above-cited experimental condition, the stimulation interrupts rapidly pancreatic fluctuations, indicating GH negative action on insulin secretion, lasting 8 sec., before pancreas size augments (=
On the contrary, in case of both diabetes constitution-dependent inherited real risk, evolution to diabetes, and overt diabetes, of course, all above-mentioned parameter values result modified in clear-cut manner, showing intense glucagone action, in relation to insulin resistance and respectively insulin deficiency. In fact, pancreas minimal size lasts less than 8 sec., indicating that glucagon secretion is rapid and intense (= pancreas subsequent increase is more than
Role of -cell insulin receptor resistance in diabetic biophysical-semeiotic constitution
To assess the effect of insulin receptor disruption on -cell function in response to physiological GH-RF stimulation, it is sufficient to ascertain parameter values of above-mentioned events, regarding the inhibition of insulin secretion and subsequent glucagon secretion increasing. In fact, under experimental circumstances, described above, exclusively in presence of diabetic constitution glucagon secretory response was more rapid (latency time: NN = 8 sec.) as well as more intense (Intensity: NN = 2cm). Soon thereafter, liver lowers quickly of
To summarise, in individuals with insulin resistance of target organs, e.g. in patients affected by pre-metabolic and metabolic syndrome, both classic and variant (36), is easy to demonstrates that -cells insulin receptor disruption is present always associated with diabetic quantum-biophysical-semeiotic constitution, proving to play a central role in glucose metabolism disorders.
1)Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986
2) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
3) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico- Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/libro_costituzionisemeiotiche.htm
4) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Travel Factory, Roma, 2005. http://www.travelfactory.it/libro_singlepatientbased.htm
5) Stagnaro S. Pivotal role of Biophysical Semeiotic Constitutions in Primary Prevention. Cardiovascular Diabetology, 2:1, 2003 http://www.cardiab.com/content/2/1/13/comments#5753
6) Stagnaro S. Stagnaro Sergio. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1. See also
7) Stagnaro S.,
8) Stagnaro Sergio. New bedside way in Reducing mortality in diabetic men and women. Ann. Int. Med.2007. http://www.annals.org/cgi/eletters/0000605- 200708070-00167v1
9) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. http://medicine.plosjournals.org/perlserv/?request=read-response 2005
10) Stagnaro Sergio. Bedside Biophysical-Semeiotic Osteocalcin Test in Diagnosing and Monitoring Diabetes. The Lancet, January 28, 2008. http://www.thelancet.com/journals/lancet/article/PIIS0140673608601014/comments?action=view&totalComments=2
11) Stagnaro Sergio. Il test Semeiotico-Biofisico della Osteocalcina nella prevenzione primaria del diabete mellito. www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=909&Itemid=47
12) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775
13) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale – Acta Med. Medit. 13, 99
14) Stagnaro-Neri M., Stagnaro S., Il Segno di Bilancini-Lucchi nella diagnosi clinica del diabete mellito. The Pract. Ed. It. 176, 30, 1993.
15) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.
16) Dan Kawamori,Amarnath J. Kurpad,Jiang Hu, et al. Insulin Signaling in Cells Modulates Glucagon Secretion In Vivo. Cell Metabolism, Volume 9, Issue 4, 350-361, 8 April 2009
17) (1966). Gluconeogenesis in the perfused liver. The effects of fasting, alloxan diabetes, glucagon, epinephrine, adenosine 3,5-monophosphate and insulin. Am. J.Med. 40, 709715. PubMed
18) (1977). The role of glucagon in the endogenous hyperglycemia of diabetes mellitus. Annu. Rev. Med. 28, 119130. PubMed
20) (1973). Lack of glucagon response to hypoglycemia in diabetes: Evidence for an intrinsic pancreatic alpha cell defect. Science 182, 171173. PubMed
21) (1978). Role of glucagon in the pathogenesis of diabetes: The status of the controversy. Metabolism 27, 16911709. PubMed
22) (1976). Hypertrophy and hyperplasia of somatostatin-containing D-cells in diabetes. Proc. Natl. Acad. Sci. USA 73, 13381342. PubMed
24) (1981). In vivo inhibition of glucagon secretion by paracrine beta cell activity in man. J. Clin. Invest. 68, 314318. PubMed
25) (1984). Insulin within islets is a physiologic glucagon release inhibitor. J. Clin. Invest. 74, 22962299. PubMed
26) Stagnaro Sergio. Semiotica Biofisica Quantistica. Scienza&Conoscenza, 8 Ottobre, 2008, http://www.scienzaeconoscenza.it/articolo.php?id=21568 e Terra di Nessuno. http://terradinessuno.wordpress.com/biblioteca-di-terra-di-nessuno/sergio-stagnaro-semeiotica-biofisica-quantistica/
27) Stagnaro Sergio. Benjamin Libet’s experiments: Quantum Biophysical Semeiotics view-point! The General Science Journal. 31 Dec. 2008.
28) Stagnaro Sergio. Cancro Polmonare: Diagnosi Semeiotica-Biofisica-Quantistica e Terapia del Reale Rischio Congenito. www.fce.it, 17 dicembre 2008. http://www.fceonline.it/index.php?option=com_content&task=view&id=2161&Itemid=45
29) Sergio. Diagnosi Clinica del Reale Rischio Oncologico Congenito con
30) Stagnaro Sergio e Manzelli Paolo. Semeiotica Biofisica Quantistica: Livello di Energia libera tessutale e Realtà non locale nei Sistemi biologici. www.fce.it , 29 maggio 2008, http://www.fcenews.it/index.php?option=com_content&task=view&id=1421&Itemid=47
31) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica, 2007. http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5243
32) Stagnaro Sergio e Paolo Manzelli, 09-1-2008, Semeiotica Biofisica Quantistica: la manovra di attivazione surrenalica jatrogenetica http://www.fcenews.it/index.php?option=com_content&task=view&id=161&Itemid=63
33) Stagnaro Sergio e Paolo Manzelli. L’Esperimento di Lory. Scienza e Conoscenza, N° 23, 13 Marzo 2008. http://www.scienzaeconoscenza.it//articolo.php?id=17775
34) Stagnaro Sergio. Melanoma? Escluso in 1 Secondo con
35) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Endocrinologica: Meccanica Quantistica e Meccanismi d’Azione Ormonali. Dicembre 2007, www.fce.it, http://www.fcenews.it/index.php?option=com_content&task=view&id=816&Itemid=45
36) Stagnaro Sergio. Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes. Eur J Clin Nutr. 2007 Feb 7; [PubMed]
* Sergio Stagnaro MD
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Founder of Quantum Biophysical Semeiotics
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