Lactate Production from the Rat Hindlimb Is Increased After Glucose-Administration and Is Suppressed by a Selective Amylin Antagonist: Evidence for Action of Endogenous Amylin in Skeletal Muscle

Vine, William; Smith, Peter J.; R, LaChappell; Rink, T J; Young, Andrew

doi:10.1006/bbrc.1995.2658

Cited by 14 publications

(6 citation statements)

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“…This could explain why several researchers have not observed cAMP as a mediator of amylin action and could therefore explain some of the discrepancies in the literature (5,16). We conclude that SCT-(8-32) is an effective antagonist of amylin-activated glycogenolysis and lactate efflux, a view which supports the use of compounds based on this peptide as inhibitors of the Cori cycle for controlling blood glucose in NIDDM (29,31). However, such compounds may not be effective in attenuating amylin inhibition of insulin-stimulated glucose uptake and would therefore not be expected to reduce peripheral insulin resistance.…”

Section: E10mentioning

confidence: 61%

“…These observations further support our contention that the action of amylin may gradually increase with time. The SCT-(8-32) analog AC-187 has been shown to attenuate lactate efflux from muscle (29), and we have demonstrated that SCT- is also effective in eliminating this amylininduced lactate efflux (Figs. 4 and 5).…”

Section: E8 Amylin Regulates Glycolysismentioning

confidence: 78%

“…However, several in vivo studies have suggested that amylin is effective at physiological concentrations. Vine et al (29) demonstrated that an antagonist based on SCT-(8-32) was able to decrease lactate efflux across the rat hindlimb. Frontoni et al (7) demonstrated that plasma concentrations of 300 pM could change the fraction of plasma glucose that was partitioned to glycogen and glycolysis in muscle.…”

Section: E10mentioning

confidence: 99%

“…This observation would suggest that the in vivo measurement of amylin concentration may not be reliable. Regardless of the physiological role of amylin, understanding its mechanism of action is very important, because amylin agonists and antagonists are being developed for use in humans (14,29).…”

Section: E10mentioning

confidence: 99%

“…It was originally isolated from amyloid plaque formations in type II diabetics and has been shown to inhibit insulinmediated glucose uptake and disposal in muscle and to raise blood lactate (4,26). Although the actual role of amylin is unclear, it has been suggested that amylin agonists may be helpful in preventing hyperinsulinemic shock in insulin-dependent diabetes mellitus and that amylin antagonists, such as salmon calcitonin- [SCT-(8}32)], may be useful in increasing blood glucose uptake into muscle in the non-insulin-dependent diabetes mellitus (NIDDM) patient (26,29,31).…”

mentioning

confidence: 99%

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Amylin influences insulin-stimulated glucose metabolism by two independent mechanisms

Castle

Kuo

Ivy

1998

American Journal of Physiology-Endocrinology and Metabolism

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The effects of amylin on fiber type-specific muscle glucose metabolism under hyperglycemic (10 mmol/l) and hyperinsulinemic (2.1 nmol/l) conditions were investigated using a rat hindlimb perfusion system. Amylin concentration ranged from 1 to 100 nM. Efficacy for inhibition of glucose uptake traced with 2-deoxyglucose by amylin was demonstrated in all three fiber types. The incorporation of 2-deoxy-[3H]glucose tracer decreased from control values by 41% in fast oxidative (FO), 36% in fast glycolytic (FG), and 37% in slow oxidative (SO) muscle with 100 nM amylin. Amylin increased intracellular glucose 6-phosphate (G-6- P), and G-6- P was negatively correlated with 2-deoxyglucose uptake in both FO ( r = −0.65; P < 0.01) and FG ( r = −0.53; P < 0.01) muscle. Muscle glycogen concentration increased under control conditions and decreased in the presence of 100 nM amylin. Lactate arteriovenous efflux across the hindlimb increased significantly above control with 100 nM amylin (5.03 ± 0.81 to 11.28 ± 0.94 μmol ⋅ g−1 ⋅ h−1). Adenosine 3′,5′cyclic monophosphate (cAMP) increased in FO and FG muscle with amylin. Salmon calcitonin-(8—32), an amylin antagonist, ameliorated the effect of amylin on all responses other than 2-deoxyglucose uptake and G-6- Pconcentration. These results suggest that amylin may work through at least two independent mechanisms, a cAMP-mediated effect on glycogen metabolism and a non-cAMP-mediated inhibition of glycolysis.

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Section: E10mentioning

confidence: 61%

Section: E8 Amylin Regulates Glycolysismentioning

confidence: 78%

Section: E10mentioning

confidence: 99%

Section: E10mentioning

confidence: 99%

mentioning

confidence: 99%

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Amylin influences insulin-stimulated glucose metabolism by two independent mechanisms

Castle

Kuo

Ivy

1998

American Journal of Physiology-Endocrinology and Metabolism

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Acetyl-[Asn30,Tyr32]-calcitonin fragment 8-32 forms channels in phospholipid planar lipid membranes

et al. 2007

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The N-terminally truncated derivative of salmon calcitonin (sCt) (acetyl-[Asn(30),Tyr(32)]-calcitonin fragment 8-32) (AC 187) lacks hormonal activity and is a potent and selective antagonist of the hormone and amylin receptor. It was investigated for its capability to interact and form channels in palmitoleoylphosphatidylcholine:dioleoylphosphatidylglycerol planar lipid membranes. Interestingly, AC 187 exhibits channel activity, whose parameters, i.e., central conductance (Lambda (c)), occurrence (number of channels/min), voltage-dependence and lifetime, are similar to those found for sCt although, in the same experimental conditions, it takes longer to incorporate into the membrane than sCt. This channel activity can be modulated by changing either the holding potential or the pH of the medium, or by adding picomolar concentrations of SDS. One evident difference between the two peptides is that sCt is unselective (1.03) while AC 187 displays a cationic selectivity (P (K) (+)/P (Cl) (-) = 2.7) at pH 7, increasing to 3.87 when the pH drops to 3.8. The present findings indicate that the 1-7 disulfide bridge is sufficient but not necessary for membrane interaction, in accordance with the observation reported on the interaction with membrane receptors. Furthermore, the remarkable pH dependence of the cationic channel could be taken into consideration for full biotechnological study.

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Receptor autoradiography as mean to explore the possible functional relevance of neuropeptides: focus on new agonists and antagonists to study natriuretic peptides, neuropeptide Y and calcitonin gene-related peptides

2004

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Lactate Production from the Rat Hindlimb Is Increased After Glucose-Administration and Is Suppressed by a Selective Amylin Antagonist: Evidence for Action of Endogenous Amylin in Skeletal Muscle

Cited by 14 publications

References 0 publications

Amylin influences insulin-stimulated glucose metabolism by two independent mechanisms

Amylin influences insulin-stimulated glucose metabolism by two independent mechanisms

Acetyl-[Asn30,Tyr32]-calcitonin fragment 8-32 forms channels in phospholipid planar lipid membranes

Receptor autoradiography as mean to explore the possible functional relevance of neuropeptides: focus on new agonists and antagonists to study natriuretic peptides, neuropeptide Y and calcitonin gene-related peptides

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