EFFECTS OF MONOSACCHARIDES AND DISACCHARIDES ON
BETA CELLS OF ISLETS OF LANGERHANS
S. T. NERENBERG, M.D.
Department of Pathology, University of Minnesota, Minneapolis, Minnesota
It has previously been demonstrated by means of bioassay that the secretion
of insulin by the islets of Langerhans stops when an animal is starved4 or given
exogenous insulin.3 Associated with the loss of endogenous insulin is a loss of
granulation of the beta cells.1 Much evidence supports the idea that the beta
granules represent stored insulin.2
We have previously shown that pure carbohydrate or carbohydrate-containing
foods stimulate regranulation of beta cells degranulated by either starvation or
exogenous insulin.8 As yet, no one has studied the effect of the various individual
carbohydrates on the beta cells. This work seems especially indicated since recent
reports have suggested that the monosaccharide, fructose, is metabolized by
man and animal without the need of insulin.9
The present study was undertaken to compare the ability of specific monosaccharides and disaccharides to stimulate regranulation of degranulated beta cells.
In addition, a noncarbohydrate substance, olive oil, was utilized as a control
substance for comparison with the carbohydrates. The carbohydrates were given
in 2 ways, by gastric tube, and subcutaneously, to compare the effects of the
different methods of administration. The effect of parenteral administration of
disaccharides was especially interesting, since these carbohydrates are not broken
down by the body as they are when given orally. One would then expect a difference in response by the beta cells to the disaccharides given by these 2 methods.
The olive oil was given only orally.
The carbohydrates administered were glucose, galactose, fructose, sucrose
and lactose.
EXPERIMENTAL METHOD
Approximately 250 rats of the Sprague-Dawley strain, weighing between 75
and 150 grams each, were given 4 units of protamine zinc insulin per 75 gi'ams of
body weight for 14 days. The pancreas of each survivor (approximately 50 per
cent) was then biopsied. One hundred and ten of the rats were divided into 11
groups of 10 rats each. The animals were all starved except that each group received one of the carbohydrates already mentioned. One rat from each of the
groups was killed each day. Each pancreas was fixed in 4 per cent formalin and
stained with our modification of Gomori's chrome-alum-hematoxylin stain 6 for
the demonstration of beta granules.
Received for publication April 15, 1953.
This work was done under the guidance of Dr. E. T. Bell, Professor Emeritus, Department of Pathology, University of Minnesota. The work was supported by a grant from
the U. S. Public Health Service.
Dr. Nerenberg is Instructor.
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NERENBERG
Each of the first 5 groups received 1 of the carbohydrates (glucose, galactose,
fructose, sucrose and lactose) by stomach tube as a 50 per cent solution, 5 ml.
twice a day. The second 5 groups received 1 of the carbohydrates subcutaneously
as a 10 per cent solution, 20 ml. twice a day. The eleventh group (control group)
received 5 ml. of olive oil by stomach tube twice a day.
RESULTS
All the groups receiving carbohydrate by stomach tube are discussed together,
since the beta cells showed identical changes. Hydropic changes in the beta cells
were observed the first few days after the carbohydrate feeding was begun. These
changes were most marked during the second and third days, gradually disappearing after the fourth day, but occasionally persisting to the sixth day. The
beta granules first appeared on the second day. The beta cells appeared to have
their full complement of granules by the fourth day. Some variation in the return
of granules was noted between the groups but this was similar to the variations
within the same group. For instance, an occasional animal showed less granulation on the sixth day than one killed on the fifth day. The variations were slight.
All groups showed similar hydropic changes and return of the beta granules.'
Groups receiving glucose and galactose subcutaneously. These animals showed
essentially similar changes to those observed with the intragastric administration
of these carbohydrates.
Group receiving fructose subcutaneously. This group of animals showed almost
identical changes to those observed with the intragastric administration of glucose. Hydropic changes of the beta cells were observed the first 3 days. Beta
granulation was pronounced by the third day and the beta cells appeared to be
completely granulated by the fourth day.
Groups receiving sucrose and lactose subcutaneously. These rats showed no return
of beta granulation during the time of the experiment (10 days). The beta cells
for the most part appeared to be shrunken, with little cytoplasm about the nuclei. Other beta cells were surrounded by a normal amount of cytoplasm, which
was devoid of granules. Many islets were very small and the alpha cells appeared
unaffected.
The zymogen granules gradually disappeared from the acinar cells, so that
none were present in the animals killed during the latter part of the experiment.
This change was observed in all groups.
Group receiving olive oil by stomach tube. None of these rats showed any return
of beta-cell granulation during the length of the experiment. The beta cells were
similar in appearance to those described for the groups receiving lactose and
sucrose subcutaneously.
DISCUSSION
It is to be expected that both the monosaccharides and disaccharides would
act similarly on the beta cells when given by stomach tube, since it is well known
that the intestine breaks down the disaccharides into monosaccharides, which
are then utilized. It is interesting to note that fructose, which has been reported
BETA CELLS OF PANCREAS
1001
as being metabolized without the need of insulin,9 acted similarly to glucose,
whether the fructose was administered subcutaneoiisly or by gastric tube. I t
should be emphasized that this observation does not necessarily indicate that
fructose needs insulin for its metabolism, but only that it stimulates the secretion
of insulin by the beta cells. One possible explanation for this may be that a portion of the fructose is converted into glucose9 or that it stimulates a greater release of glucose from the liver.5
The fact that the disaccharides when given subcutaneoiisly do not stimulate
the secretion of insulin is interesting and not unexpected. One wonders whether
it is the aldehyde grouping or some other chemical grouping of the carbohydrate
that specifically stimulates the beta cells to secrete insulin.
The failure of olive oil to stimulate regranulation of the degranulated beta
cells is also not unexpected and suggests that the beta cells are only sensitive to
monosaccharides or substances that will form monosaccharides.
I t is hoped that as increased information becomes available concerning the
effects of the various components in our diet on the beta cells, a better understanding of the basic physiology of these cells will result.
SUMMARY
Both monosaccharides and disaccharides given by mouth stimulate the secretion of insulin by the beta cells of the islets of Langerhans.
Monosaccharides given parenterally act similarly to those administered intragastrically. This group includes fructose, which has been reported as beingmetabolized in the animal body without the need of insulin.
Disaccharides given parenterally or olive oil given intragastricall.y does not
stimulate the secretion of insulin by the beta cells of the islets of Langerhans.
REFERENCES
1. BARRON, S. S.: Significance of the beta granules in the islets of Langerhans of the pancreas. Arch. Path., 46: 159-163, 1948.
2. BELL, E. T.: The incidence and significance of degranulation of the beta cells in the
islets of Langerhans in diabetes mellitus. Diabetes, 2: 125-129, 1953.
3. BEST, C. II., AND HAIST, R. E.: The effect of insulin administration on the insulin content of the pancreas. J. Physiol., 100: 142-146, 1941.
4. BEST, C. H., HAIST, R. E., AND RIDOUT, J. H.: Diet and the insulin content of pan-
creas. J. Physiol., 97: 107-119, 1939.
5. CRAIG, J. W., DRUCKER, VV. R., MILLER, M., OWENS, J. E., WOODWARD, H., BROFMAN,
B., AND PRITCHARD, W. H.: Metabolism of fructose by the liver of diabetic and nondiabetic subjects. Proc. Soc. Exper. Biol. & Med., 78: 698-702, 1951.
6. NERENBERO, S. T.: A modification of Gomori's stain for the demonstration of beta
granules in the islets of Langerhans. Diabetes, 2: 130-132, 1953.
7. NERENBERO, S. T.: Experimental hydropic changes in the beta cells of the islets of
Langerhans not associated with diabetes mellitus. Arch. Path., in press.
8. NERENBERO, S. T.: Regranulation of the beta cells of the islets of Langerhans following
insulin and starvation. Am. J. Clin. Path., 23: 340-342, 1953.
9. MILLER, M., DRUCKER, VV. R., OWENS, J. E., CRAIG, J. W., AND WOODWARD, H.: Me-
tabolism of intravenous fructose and glucose in normal and diabetic subjects. J. Clin.
Investigation, 31: 115-125, 1952.
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