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Of antisense, antibodies, K+ channels, and jejunal metabolism.

Adler EM - J. Gen. Physiol. (2013)

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Affiliation: eadler@rockefeller.edu

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This month’s installment of Generally Physiological focuses on endogenous regulation of K channels by antisense, K channel targeting by antibodies, and the effects of gastric bypass surgery on metabolism... A decrease in the abundance of voltage-dependent K channels in dorsal root ganglion (DRG) neurons can result in enhanced excitability and aberrant firing, contributing to neuropathic pain after peripheral nerve injury (see )... Noting that long noncoding RNAs have been implicated in the regulation of gene expression, determined that the DRG of various mammals contained long noncoding RNA transcripts (Kcna2 antisense RNA) complementary to the RNA encoding the voltage-dependent potassium channel Kcna2... Antisense, antibodies, K channels, and the effects of gastric bypass surgery on metabolism Kcna2 is only one of the many voltage-gated K (Kv) channels present in electrically excitable cells... In this issue, in an ingenious approach to this problem, Sack et al. attached a porphyrin moiety to a monoclonal antibody directed against an epitope on the external face of the Kv4.2 channel to create an immunotoxin selectively targeted to Kv4.2... The unconjugated antibody did not itself inhibit Kv4.2 current; however, patch-clamp analysis of cells heterologously expressing Kv channels indicated that, after incubation with the antibody–porphyrin conjugate, photostimulation irreversibly inhibited Kv4.2 current... Moreover, the study by provides proof-of-principle of a viable technique for using monoclonal antibodies to selectively target and inhibit individual Kv channel subtypes... Gastric bypass surgery provides an effective approach to treating obesity-related diabetes and, remarkably, glucose homeostasis improves even before substantial weight loss has taken place... Noting that rodent and human studies have indicated that the Roux limb undergoes hypertrophy and hyperplasia, used a rat model of RYGB to investigate the mechanism of enhanced glycemic control... Comparisons of the metabolic profile and patterns of gene and protein expression of the Roux limb compared with that in sham-operated rats indicated that the Roux limb underwent metabolic reprogramming of glucose metabolism, consistent with increased anabolic demands associated with the increased growth of the reconfigured segment... Positron emission tomography-computed tomography (PET/CT) scanning using 2-deoxy-2-[18F]fluoro-d-glucose ([18f]FDG) indicated that there was an increase in intestinal glucose uptake, and biodistribution analysis indicated that, after RYGB, the intestine became a major tissue for glucose use... Experiments in which a section of jejunum was interposed between the esophagus and stomach (without the other anatomical changes involved in RYGB) were consistent with the hypothesis that the morphological and metabolic changes found with RYGB were triggered by exposure of the Roux limb to undigested nutrients... The authors thus propose that morphological and metabolic changes in the Roux limb secondary to exposure to undigested food contribute to the improvement in glycemic control after gastric bypass surgery.

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Photostimulation of a porphyrin-conjugated monoclonal antibody targeted to Kv4.2. (From Sack et al., 2013.)
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fig2: Photostimulation of a porphyrin-conjugated monoclonal antibody targeted to Kv4.2. (From Sack et al., 2013.)


Of antisense, antibodies, K+ channels, and jejunal metabolism.

Adler EM - J. Gen. Physiol. (2013)

Photostimulation of a porphyrin-conjugated monoclonal antibody targeted to Kv4.2. (From Sack et al., 2013.)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3753609&req=5

fig2: Photostimulation of a porphyrin-conjugated monoclonal antibody targeted to Kv4.2. (From Sack et al., 2013.)

View Article: PubMed Central - HTML - PubMed

Affiliation: eadler@rockefeller.edu

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

This month’s installment of Generally Physiological focuses on endogenous regulation of K channels by antisense, K channel targeting by antibodies, and the effects of gastric bypass surgery on metabolism... A decrease in the abundance of voltage-dependent K channels in dorsal root ganglion (DRG) neurons can result in enhanced excitability and aberrant firing, contributing to neuropathic pain after peripheral nerve injury (see )... Noting that long noncoding RNAs have been implicated in the regulation of gene expression, determined that the DRG of various mammals contained long noncoding RNA transcripts (Kcna2 antisense RNA) complementary to the RNA encoding the voltage-dependent potassium channel Kcna2... Antisense, antibodies, K channels, and the effects of gastric bypass surgery on metabolism Kcna2 is only one of the many voltage-gated K (Kv) channels present in electrically excitable cells... In this issue, in an ingenious approach to this problem, Sack et al. attached a porphyrin moiety to a monoclonal antibody directed against an epitope on the external face of the Kv4.2 channel to create an immunotoxin selectively targeted to Kv4.2... The unconjugated antibody did not itself inhibit Kv4.2 current; however, patch-clamp analysis of cells heterologously expressing Kv channels indicated that, after incubation with the antibody–porphyrin conjugate, photostimulation irreversibly inhibited Kv4.2 current... Moreover, the study by provides proof-of-principle of a viable technique for using monoclonal antibodies to selectively target and inhibit individual Kv channel subtypes... Gastric bypass surgery provides an effective approach to treating obesity-related diabetes and, remarkably, glucose homeostasis improves even before substantial weight loss has taken place... Noting that rodent and human studies have indicated that the Roux limb undergoes hypertrophy and hyperplasia, used a rat model of RYGB to investigate the mechanism of enhanced glycemic control... Comparisons of the metabolic profile and patterns of gene and protein expression of the Roux limb compared with that in sham-operated rats indicated that the Roux limb underwent metabolic reprogramming of glucose metabolism, consistent with increased anabolic demands associated with the increased growth of the reconfigured segment... Positron emission tomography-computed tomography (PET/CT) scanning using 2-deoxy-2-[18F]fluoro-d-glucose ([18f]FDG) indicated that there was an increase in intestinal glucose uptake, and biodistribution analysis indicated that, after RYGB, the intestine became a major tissue for glucose use... Experiments in which a section of jejunum was interposed between the esophagus and stomach (without the other anatomical changes involved in RYGB) were consistent with the hypothesis that the morphological and metabolic changes found with RYGB were triggered by exposure of the Roux limb to undigested nutrients... The authors thus propose that morphological and metabolic changes in the Roux limb secondary to exposure to undigested food contribute to the improvement in glycemic control after gastric bypass surgery.

Show MeSH