Hyperinsulinemia and insulin resistance : What comes first ?

Background

1)	Classical explanation :
Classical explanation of diabetic pathophysiology states that obesity induced insulin resistance develops first and is followed by compensatory hyperinsulinnemia. Further insulin resistance leads to prolonged, increased secretary demand on beta cells leading to subsequent secondary beta cell failure, giving rise to hyperglycaemia and diabetes^2^.

2)	 Neurobehavioral origin hypothesis :
The Neurobehavioral origin hypothesis suggests that insulin resistance mediates a shift from muscle dependent (soldier) to brain dependent (diplomat) strategies of making a livelihood. If nutrient limitation affects intrauterine development, brain development is the least affected among all the organs^4,5^. As a result, in IUGR babies muscle weight is poor but the brain is relatively well developed. Such a person is more likely to be a successful diplomat rather than a soldier and insulin resistance is adaptive for such an individual^3^. Since insulin is involved in brain development and cognitive functions, higher levels of insulin are needed. As insulin is having strong anti-lipolytic effect, hyperinsulinnemia is followed by subsequent excess fat accumulation. Also compensatory insulin resistance is needed to avoid hypoglycemia. This hypothesis predicts a reverse order of pathophysiology i.e. primary hyperinsulinnemia followed by compensatory insulin resistance^3^

Objective-
To determine in diabetes whether hyperinsulinnemia develops first or insulin resistance develops first.

Methods :
We searched literature for studies that investigated directly or indirectly the sequence of development of hyperinsulinnemia and insulin resistance in humans and animal models from an early stage. Meta-analysis was conducted on published data.

Results-
1)	In low birth weight neonates in humans as well as in rat models, hyperinsulinnemia is found at very early stage.^6^
2)	Development of insulin resistance is preceded by hyperinsulinnemia in mice, rats as well as in humans.^7, 8^
3)	In normoglycaemic hyperinsulinemia state if insulin production is suppressed insulin sensitivity increases rapidly maintaining the normoglycaemic state.^9,10^
4)	Beta cell expansion beginning in intrauterine life is independent of glucose, Insulin and Insulin receptors.^6^


Conclusion-
All the four lines of evidence indicate that hyperinsulinnemia precedes insulin resistance supporting the predictions of neurobehavioral origin hypothesis over the orthodox view.



References :
1)	DeFronzo RA, Ferrannini E (1991). Diabetes Care 14:173-194
2)	Kruszynska YT, Olefsky JM (1996). J Investig Med 44: 413-428.
3)	Watve MG, Yajnik CY (2007). BMC Evolutionary Biology.7: 61-74.
 4) Winick M, Rosso P, Waterlow JC (1970). Exp Neurol, 26:393-400.
 5) Winick M. (1969) J Pediatr,74:667-679.
 6) Chakravarthy MV et.al. (2008) Diabetes, 57:2698-2707.
 7) Ramin A et. al. (1998) J Clin Endo and Met, 83 :1911-1915.
 8) Hansen BC (1990) Am J Physiol Regul Integr Comp Physiol 259: 612-617.
 9) Stanley L (1981) Life Sciences, 28: 1829-1840.
 10) Ratzmann KP et. al. (1983) Int J Obes, 7 : 453-458

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Inflating in a Trough: Single-Field Effective Theory from Multiple-Field Curved Valleys

We examine the motion of light fields near the bottom of a potential valley in a multi-dimensional field space. In the case of two fields we identify three general scales, all of which must be large in order to justify an effective low-energy approximation involving only the light field, $\ell$. (Typically only one of these -- the mass of the heavy field transverse to the trough -- is used in the literature when justifying the truncation of heavy fields.) We explicitly compute the resulting effective field theory, which has the form of a $P(\ell,X)$ model, with $X = - 1/2(\partial \ell)^2$, as a function of these scales. This gives the leading ways each scale contributes to any low-energy dynamics, including (but not restricted to) those relevant for cosmology. We check our results with the special case of a homogeneous roll near the valley floor, placing into a broader context recent cosmological calculations that show how the truncation approximation can fail. By casting our results covariantly in field space, we provide a geometrical criterion for model-builders to decide whether or not the single-field and/or the truncation approximation is justified, identify its leading deviations, and to efficiently extract cosmological predictions.Comment: 28 pages + 3 appendices, references added and typos corrected, matches published versio

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Endophytic Mycoflora of Indian Medicinal Plant, Terminalia arjuna and their Biological Activities

Studies were undertaken to isolate, identify and evaluate the biological activities of endophytic mycoflora of Indian medicinal plant, Terminalia arjuna. A total of 20 isolates of endophytic fungi were obtained from the leaves, twigs and bark tissues of the Terminalia arjuna. Out of 20, six isolates exhibited promising antibacterial, antifungal and anti-inflammatory activities when cultivated at shake flask level. The selected isolates were identified on the basis of morphology and ITS gene sequencing. Three isolates, designated as TA BA 1, TA L1 and TA L2 were identified as Aspergillus flavus whereas; the remaining three endophytic fungi were identified as Diaporthe arengae (TA TW2), Alternaria Sp. (TA TW1) and Lasiodiplodia theobromae (TA BA2). Aspergillus flavus was found as the predominant endophyte in leaves and bark tissues of the plant. The crude extract of the test isolates showed considerable antimicrobial activity against common human bacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella abony and Bacillus subtilis) and fungal (Candida albicans, Aspergillus niger and Penicilium sp.) pathogens. The extract of Diaporthe arengae (TA TW2) significantly reduced the concentration of DPPH free radical as percent DPPH scavenging activity was found to be highest (69.56%) in comparison with other isolates. The % inhibition of hemolysis of RBCs was found to be highest (82.85%) with Diaporthe arengae (TA TW2) in comparison (83.26%) with standard drug (Ibuprofen). Among all, the extract of the Diaporthe arengae (TA TW2) showed excellent biological activities and hence was subjected to further characterization. The phytochemical investigation of the extract revealed the presence of terpenoids as the major phytoconstituents which was supported by TLC and UV spectroscopic studies. The results indicate that the isolated endophytes could be the valuable source of these bioactive molecules with diverse biological activities. The bioactivities may be attributed to the terpenoids present in the endophytic extract

Evolution of the Kondo resonance feature and its relationship to spin-orbit coupling across the quantum critical point in Ce2Rh{1-x}CoxSi3

We investigate the evolution of the electronic structure of Ce2Rh{1-x}CoxSi3 as a function of x employing high resolution photoemission spectroscopy. Co substitution at the Rh sites in antiferromagnetic Ce2RhSi3 leads to a transition from an antiferromagnetic system to a Kondo system, Ce2CoSi3 via the Quantum Critical Point (QCP). High resolution photoemission spectra reveal distinct signature of the Kondo resonance feature (KRF) and its spin orbit split component (SOC) in the whole composition range indicating finite Kondo temperature scale at the quantum critical point. We observe that the intensity ratio of the Kondo resonance feature and its spin orbit split component, KRF/SOC gradually increases with the decrease in temperature in the strong hybridization limit. The scenario gets reversed if the Kondo temperature becomes lower than the magnetic ordering temperature. While finite Kondo temperature within the magnetically ordered phase indicates applicability of the spin density wave picture at the approach to QCP, the dominant temperature dependence of the spin-orbit coupled feature suggests importance of spin-orbit interactions in this regime.Comment: 6 figure

Response of Two Sunflower (Helianthus Annuus L.) Genotypes to Va-mycorrhizal Inoculation and Phosphorus Levels

The performance of two sunflower genotypes (Morden and MSFH-8) with and without VA-mycorrhizal fungi at three P levels (38, 56 and 75 kg P2O5 ha-1) in vertisol of Dharwad was studied to determine the effect of mycorrhizal inoculation on plant growth, yield and P uptake. The results showed that the VAM inoculation increased sunflower yield (14%), total biomass (16%), oil content (3.1%) and P uptake (30.5%) over uninoculated control. The percent root colonization and chlamydo-spore count decreased with increasing P levels. The total biomass production, seed yield and P uptake of mycorrhizal plants at 38 kg P2O5 ha-1 more than the non-mycorrhizal plants at 75 kg P2O5 ha-1. The biomass and seed yield of mycorrhizal plants at same P level were more than the non-mycorrhizal plants. Mycorrhizal plants of Morden at 38 kg P2O5 ha-1 and MSFH-8 at 56 kg P2O5 ha-1 produced higher seed yield, oil content and total biomass than non-mycorrhizal plants supplied with 75 kg P2O5 ha-1. The results indicated that, VA-mycorrhizal inoculation helps in saving 25 and 50 percent of recommended dose of phosphatic fertilizer (75 kg P2O5 ha-1) in MSFH-8 (single cross hybrid) and Morden (open pollinated variety), respectively

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Diaphragmatic hernia following oesophagectomy for oesophageal cancer – Are we too radical?

Background: Diaphragmatic herniation (DH) of abdominal contents into the thorax after oesophageal resection is a recognised and serious complication of surgery. While differences in pressure between the abdominal and thoracic cavities are important, the size of the hiatal defect is something that can be influenced surgically. As with all oncological surgery, safe resection margins are essential without adversely affecting necessary anatomical structure and function. However very little has been published looking at the extent of the hiatal resection. We aim to present a case series of patients who developed DH herniation post operatively in order to raise discussion about the ideal extent of surgical resection required. Methods: We present a series of cases of two male and one female who had oesophagectomies for moderately and poorly differentiated adenocarcinomas of the lower oesophagus who developed post-operative DH. We then conducted a detailed literature review using Medline, Pubmed and Google Scholar to identify existing guidance to avoid this complication with particular emphasis on the extent of hiatal resection. Discussion: Extended incision and partial resection of the diaphragm are associated with an increased risk of postoperative DH formation. However, these more extensive excisions can ensure clear surgical margins. Post-operative herniation can be an early or late complication of surgery and despite the clear importance of hiatal resection only one paper has been published on this subject which recommends a more limited resection than was carried out in our cases. Conclusion: This case series investigated the recommended extent of hiatal dissection in oesophageal surgery. Currently there is no clear guidance available on this subject and further studies are needed to ascertain the optimum resection margin that results in the best balance of oncological parameters vs. post operative morbidity