Evidence for a glutamate receptor of the AMPA subtype which mediates insulin release from rat perfused pancreas

Abstract

The effect of l‐glutamate has been studied on insulin secretion by the isolated perfused pancreas of the rat. The glutamate receptor subtype involved has been characterized. In the presence of a slightly stimulating glucose concentration (8.3 mm), l‐glutamate (5 × 10−5−4 × 10−3 m) induced an immediate, transient and concentration‐dependent insulin response. On the other hand, in the presence of a non stimulating glucose concentration (2.8 mm), l‐glutamate (10−3 m) did not modify the basal insulin secretion. The three non‐NMDA receptor agonists, kainate (10−4−10−3 m), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 5 × 10−5−10−4 m) and quisqualate (5 × 10−6−5 × 10−5 m) all provoked a transient and concentration‐dependent insulin response from pancreas perfused with 8.3 mm glucose. Compared with glutamate, kainate exhibited a similar efficacy, whereas AMPA and quisqualate elicited only a 3 fold lower maximal insulin response. In contrast, NMDA (10−4−10−3 m) was ineffective. An antagonist of non‐NMDA receptors, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX; 5 × 10−5 m) totally prevented the stimulatory effect of l‐glutamate (4 × 10−4 m) and kainate (2 × 10−4 m). In contrast, the NMDA receptor antagonist, (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5,10‐imine ((+) MK801) was without effect. The insulin secretory effect of glutamate (4 × 10−4 m) was not affected by atropine (3 × 10−7 m) or tetrodotoxin (3 × 10−6 m). Quisqualate at a high maximally effective concentration (4 × 10−4 m) inhibited glutamate (10−3 m) or kainate (4 × 10−4 m)‐induced insulin release. This study shows that l‐glutamate stimulates insulin secretion in rat pancreas, by acting on an excitatory amino acid receptor of the AMPA subtype.

Secretory Granule-mediated Co-secretion ofl-Glutamate and Glucagon Triggers Glutamatergic Signal Transmission in Islets of Langerhans

“…Several works have reported that L-glutamate or agonists of glutamate receptor stimulate to some extent the secretion of insulin under high glucose conditions in cultured cells, isolated islets, and perfused pancreas (4,6,7,9). Consistently, we observed that L-glutamate slightly stimulates (ϳ10%) insulin secretion from MIN6 m9 cells (Fig.…”

“…Another significant finding obtained in the present study is that the L-glutamate signaling triggers GABAergic response in clonal ␤ cells and isolated islets. The released L-glutamate may bind to the corresponding receptors on the islet cells, causing a paracrine or autocrine response (3)(4)(5)(6)(7)(8)(9)(10)(11). Islet ␤ cells contain GABA in SLMVs at concentrations comparable level to the central nervous systems (36,37).…”

A Review of Glutamate Receptors I: Current Understanding of Their Biology

“…Many tissues demonstrate Glu, GluR and GluTPs, including but not limited to, CNS 122 , autonomic and sensory ganglia 123 , peripheral nerves-myelinated and unmyelinated 124,125 , vagus and other cholinergic nerves 124 , tachykinin containing sensory nerves and vestibular tissues 1 2 6 , 1 2 7 retinal photoreceptors 1 2 8 -1 3 0 , Muller cells 1 2 8 , 1 3 1 , adrenal medulla 123,133 , pituitary 134 , pineal gland 135 , endocrine pancreas [136][137][138][139][140][141][142][143][144][145][146][147] , immune system 148 , taste buds 149,150 , esophagus 151 , gut 70,100,[152][153][154] , ileal longitudinal muscle [155][156][157] , h e pa to c yt e s 6 8 , 1 5 8 , k i d n e y , s p l e e n s , o v a r i e s 4 8 , 1 5 9 , lungs 60,99,145,148,154,[158][159][160][161][162][163][164][165] , heart …”

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…NMDA receptor antagonists do not discriminate between the diverse actions of the receptor, and thus interfere with both the negative and positive effects of this signaling [58,59]. Furthermore, NMDA antagonists affect glutamate transporters that reside in many extracerebral peripheral tissues, such as the pancreas, which play an important role in the metabolic regulation of glutamate [60][61][62][63][64].…”