The effect of glucose anomers upon insulin and glucagon secretion

Abstract

Summary. The precise mechanism of insulin release is unknown, though the presence of a beta cell surface receptor has been postulated. As D-glucose exists in at least two anomerie forms, ct and fl, these were employed to study insulin release in three animal models. After rapid dissolution, each anomer was rapidly injected into intact rats, dogs, and a rat pancreatic perfusion system. There was a trend toward greater insulin secretion and greater suppression of glucagon by the ~. anomer.Key words: glucose anomers, insulin release, glucagon, mutarotation.D-glucose is known to exist in the crystalline state in either the ~ or fl anomerie form. After placing either of the anomers in aqueous solution there is a transformation into an equilibrium state in which 64% is in the fl form and 36% is in the ~ form. Glucose has been shown to be a major stimulant to insulin release, although the exact mechanism is unknown. Current theories include either a direct interaction of glucose upon a receptor site on the beta cell, or a glucose metabolite which causes insulin secretion, or both. To study the effect of these two D-glucose anomers on insulin release, three different animal models were used. This preliminary survey suggests that there may be some difference between the effect of the two forms upon insulin and glucagon secretion. Materials and Methods Acute cr or fl Glucose Administration to RatsMale Charles River Strain albino rats weighing 180--200 g were fasted for 24 h prior to experimentation. They were anesthetized with intraperitoneal sodium pentobarbital (0.1 rag/100 g body weight). A midline abdominal incision was made. Surrounding tissues were dispaced laterally and the aorta and vena cave were separated. A small 3" tubing (Minicath PRlkLDeseret Cat #5084) was placed into the vena cave 3 cm below the renal vein. A stock glucose solution was prepared in sterile normal saline twelve hours prior to use to assure complete mutarotation (64% fl, 36% ~). Alpha and Beta glucose (Sigma Chemical G-5250, Beta, lot #052e-0810 analyzed as 99.2% fl and 0.8% g, and Sigma Chemical G-5000, Alpha, lot #091C-1690 analyzed as 97.6 % ~. and 2.4% fl) were each dissolved by vigorous shaking for 10 sec in sterile * Supported by U.S.P.H.S. grants AM-09748 and AM-15191 and the Joslin Diabetes Foundation, Inc. saline just prior to injection. These glucose solutions were infused over 5 sec in a volume of 1 ml at a concentration of 200 mg/ml and blood was withdrawn and flushed through the tubing three times to assure completeness of the infusion. A volume of 1 ml blood was removed at time 0, and after the infusion at 1, 3, 5 and 10 rain for glucose ~nd insulin determinations [1, 2]. Acute :r and fl Glucose Administration to DogsMongrel dogs weighing between 22 and 26 kg were employed. Twenty-four hours prior to the studies the animals were anesthetized with sodium pentobarbital (10 mg/kg) and catheters were placed into both jugular veins. The tubings were kept patent with a heparin solution (3 units/1 ml of saline). One catheter was used f...

Insulin release is glucose anomeric specific in the human.

“…For example, the greater ability of the a-glucose vs. the /3-glucose anomer in protecting the ,8-cell against the toxicity of alloxan in rats has previously been demonstrated by this laboratory (6). The capability of the a-anomer to produce a greater stimulation of insulin release than the P-anomer has been observed by our laboratory and others utilizing various animal models and techniques (7)(8)(9)(10). However, in the human, the intravenous administration of these glucose anomers (0.5 g/kg body wt over a 3-min period) has so far been unsuccessful in documenting this differential effect on insulin release (11).…”

Rapid13C NMR hyperpolarization delivered frompara-hydrogen enables the low concentration detection and quantification of sugars

“…The equilibrium distribution of these two isomers is 64% b-glucose and 36% a-glucose, when measured in water. 83 The shi in ratio observed here will reect the change in solvent. 7…”

“…This type of spin state can be created through the use of RF (radio frequency) excitation and such states may have long lifetimes. 74,75 Fig. 5a shows two different pulse sequences which can be used to achieve singlet order in the sample given that there are two coupled spins with a chemical shi difference which is typically less than 500 Hz.…”

Effects of .ALPHA.-D-mannose and equilibrated D-mannose on insulin release.

“…, as well as in vivo (Rossini et al, 1974 ;Rossini and Soeldner, 1976). Since the uptake (Idahl et al, 1975;Miwa et al, 1975), phosphorylation or further metabolism (Idahl et al, 1975 and of …”