EFFECT OF NICOTINAMIDE ON BLOOD SUGAR AND BLOOD ACETONE BODIES OF DIABETIC AND NORMAL SUBJECTS

BY SACHCHIDANANDA BANERJEE AND NARESH CHANDRA GHOSH (From the Department of Mitra Research in Diabetes, Calcutta School of Tropical

Medicine, Calcutta, India)

(Received for publication, February 3, 1948)

Gobell (1) showed that 100 mg. of nicotinamide injected intravenously into children produced regularly a fall in the blood sugar level, averaging 21.3 mg. per cent. The hypoglycemic action of nicotinic acid was also observed in normal human adults by Marche and Delbarre (2), Poumeau- Delille and Fabiani (3), and Neuwahl (4). In experiments with animals Ledrut (5) observed a marked decrease in the blood sugar level in normal rabbits which received nicotinic acid orally or intravenously. Large doses of nicotinic acid injected into rats produced hypoglycemia in the hands of Cherkes and Rozenfeld (6). Neuwahl reported (4) that an intravenous injection of 250 mg. of nicotinic acid in eight non-diabetic subjects produced a blood sugar level as low as 48 mg. per 100 cc., which led to long lasting rigor. When glucose was injected along with nicotinic acid, no reaction was observed. Horst (7), on the other hand, reported that the administra- tion of nicotinamide to persons with normal metabolism had no influence on the fasting blood sugar level or on the glucose tolerance curve. Neuwahl (4) observed a definite improvement in the carbohydrate tolerance in twelve diabetic patients receiving nicotinic acid. Gordon (8) reported a patient on a diet of 1200 calories who had a fasting blood sugar of 160 mg. per 100 cc. of blood. After the patient was fed 1200 mg. of nicotinamide per day for 1 month, the blood sugar dropped to 60 mg. per 100 cc. of blood. Contrary to the findings of Neuwahl (4) and Gordon @),Poumeau-Delille and Fabiani (3) did not notice any effect of nicotinic acid on the glycemia of diabetic patients. Wade (9) also reported that 666 mg. of nicotinamide fed thrice daily for 14 days to six diabetic patients who were receiving adequate insulin neither influenced the sugar tolerance nor improved the diabetic condition.

In view of the conflicting reports cited above and in view of the observa- tion that nicotinic acid prevents the diabetogenic action of alloxan (10) in rabbits and rats, it was thought desirable to study the effect of intra- venous injection of nicotinamide on the blood sugar and blood acetone bodies of diabetic and normal subjects.

EXPERIMENTAL

E$ect of Nicotinamide on Blood Sugar of Diabetic and Normal Subjects- 560 mg. of nicotinamide in a 10 per cent solution were injected intravenously

789

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790 NICOTINAMIDE IN DIABETES

into seventeen diabetic and six normal subjects which had fasted overnight. Samples of blood were taken before and at intervals of half an hour up to 2 hours after the injection. Blood sugar was determined by the method of Hagedorn and Jensen (11). The results are given in Table I.

TABLE I

Effect of Intravenous Injection of 600 Mg. of Nicotinamide on Blood Sugar of Diabetic and Normal Suhiects

Subject

Diabetic S. K. M. ...... J. C. B. ....... S. B. .......... S. N. B ........ S. C. G ........ B. S. .......... F. R ........... a. a. .......... R. K. G ....... R. B. S ........ N. M. ......... M. N. M ....... M. P. ......... N. A. ......... D. M. K ....... a. a. .......... K. C. D .......

-

Fasting blood sugar -

.- *hr. 1 hr. l$ hrs. 2 hrs. -

Y-. nag. per Cd

70 180 200 48 286 278 28 521 527 70 117 127 60 138 143 42 385 399 27 110 110 40 186 213 53 251 270 37 241 247 16 324 326 40 230 211 37 236 226 70 298 282 44 288 290 39 270 270 37 224 224

Average. . . . . . . . 252 i 2. 255 f 2, ___-

- - 4 _-

-.

-

Normal S. C. A ........ 45 A. M. K ....... 47 M. L .......... 30 M. J ........... 45 H. M .......... 41 S. N. M ....... 41

Average . . .

100 93 97

109 92

100

99

Blood sugar after injection of nicotimmide

-- mg. per cent mg. &r cent

189 230 514 120 140 390 110 226 245 262

186 232 278 278 270 217

195 260 534 117 143 340 116 228 232 276 328 202 222 292 264 284 195

. - 4 _ -

243 f 24 248 f 2:

199 216 550 117 143 333 134 260 257 276 297 179 221 316 280 274 195

--

250 & 23

100 103 96 105 93 93 97 93

110 117 115 122 117 126 117 112 88 93 95 84 87 100 87 87

99

-_

- 105 101 100

-7

E$ect of Nicotinamide on Blood Acetone Bodies of Diabetic and Normal Subjects-500 mg. of nicotinamide in a 10 per cent solution were injected intravenously into ten diabetic and three normal subjects which had fasted overnight. Samples of blood were taken as before. Total acetone bodies

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S. BANERJEE AND N. C. GHOSH 791

of blood were determined as follows: 1 cc. of oxalated blood was delivered into 10 cc. of distilled water taken in a 25 cc. stoppered measuring cylinder. After the laking was complete, 2 cc. of 0.3 N barium hydroxide were added and the contents well mixed by shaking. 2 cc. of a 5 per cent solution of zinc sulfate were then added. The contents were mixed and centrifuged. 10 cc. of the centrifugate were then transferred to an all-glass distilling

TABLE II

Efect of Intravenous Injection of 600 Mg. of Nicotinamide on Acetone Bodies of Blood of Normal and Diabetic Subjects

yls. Diabetic

S. K. M ....... 70 J. C. B ........ 48 S. B ........... 28 S. N. B ........ 70 S.C.G.. ...... 60 B. S ........... 42 s. s ........... 40 J.C.D.. ...... 37 J. N. S ........ 53 K. C. D ....... 37

Average ..........

Normal 5. C. A. ....... 45 A. M. K ....... 47 R. F ........... 26

Average ..........

I

-

.-

-

-

Fasting blood rcetone bodies

1.64 1.46 4.50 1.03 1.88 1.36 4.60 1.12 1 . 1.0

41.80

6.01 f r

0.95 0.59 1.20

0.91

T

L

_-

-

Blood acetone bodies after injection of nicotinamide

1.64 1.34 4.52

1.60 1.10 4.00 1.10 1.34

55.80

8.05 f f

0.96 0.64 1.20

0.93

-

_ i -

__

-

1 hr.

0.50 1.12 3.77

1.04 1.48

56.00

10.65 f !

0.60 1.31

0.95

-

4.0 1.12 2.53 0.54 1.06

8.00 1.10 1.23

56.40 ~-

8.50 f t

3.00 0.64 1.76

1.13

-

_-

5

--

-

2 hrs. ___- fug. Q6? cenl

16.8 0.88 2.25

1.30 3.45

10.32 1.08 1.06

40.00

8.57 i 4

1.46

2.77

1.41

apparatus with only one ground glass joint and 10 cc. of distilled water were added. The distilling 3ask was heated on a micro burner. 0.46 per cent potassium dichromate in 15.6 N sulfuric acid was added drop by drop, from a dropping funnel attached to the middle of the neck of the flask, when the contents of the flask began to boil. The distillation was continued for 20 minutes, and the distillate was collected into a conical flask containing 2 cc. of distilled water. An aliquot of the distillate was allowed to react with 2,4dinitrophenylhydrazine and the total acetone bodies were es- timated as described by Greenberg and Lester (12). The results are given in Table II.

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792 NICOTINAMIDE IN DIABETES

From the results it will be seen that nicotinamide had practically no effect on the blood sugar and blood acetone bodies of diabetic and normal subjects. The claim of Gobell (l), therefore, could not be confirmed.

SUMMARY

The effect of intravenous injection of 500 mg. of nicotinamide on the blood sugar and blood acetone bodies of diabetic and normal subjects has been studied.

The blood sugar and the blood acetone bodies are practically unaffected by the injection of nicotinamide in both diabetic and normal subjects.

The authors are indebted to N. P. Chatterjee of the East India Pharma- ceutical Works, Calcutta, for the nicotinamide and to the Indian Research Fund Association for a research grant.

BIBLIOGFiAPHY

1. Gobell, O., 2. ges. ezp. Med., 109, 96 (1941). 2. Marche, J., and Delbarre, F., Compt. rend. Sot. biol., 157, 153 (1943). 3. Poumeau-Delille, G., and Fabiani, Compt. rend. Sot. biol., 157. 235 (1943). 4. Neuwahl, F. J., Lancet, 2,349 (1943). 5. Ledrut, J., Bull. Sot. chim. biol., 22,321 (1940). 6. Cherkes, L. A., and Rozenfeld, E. L., Biokhimiya, 6,!53 (1941). 7. Horst, H. G., Vitamine u. Hormone, 1, 269 (1941). 8. Gordon, W., Brit. Med. J., 1,218 (1946). 9. Wade, H. J., B&!. Med. J., 1.414 (1947).

10. Banerjee, S., Science, 106, 128 (1947). 11. Hagedorn, H. C., and Jensen, B. N., Biochem. Z., 137,92 (1923). 12. Greenberg, L. A., and Lester, D., J. Biol. Chem., 164, 177 (1944).

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GhoshSachchidananda Banerjee and Naresh Chandra

SUBJECTSBODIES OF DIABETIC AND NORMAL

ACETONEBLOOD SUGAR AND BLOOD EFFECT OF NICOTINAMIDE ON

1949, 177:789-792.J. Biol. Chem. 

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