Norman H. Ertel

A Comparison of Carbohydrate Metabolism After Sucrose, Sorbitol, and Fructose Meals in Normal and Diabetic Subjects

Sucrose, sorbitol, and fructose (35 g) were fed to normal and diabetic subjects as a component of a 400-calorie breakfast. In both normal and diabetic subjects, the mean peak increment in plasma glucose was highest after the sucrose meals (44.0 mg/dl for normal subjects; 78.0 mg/dl for diabetic subjects); lowest after sorbitol meals (9.3 mg/dl for normal subjects; 32.3 mg/dl for diabetic subjects); and intermediate after the fructose meals (29.0 mg/dl for normal subjects; 48.0 mg/dl for diabetic subjects). In normal subjects, the mean peak increment of plasma immunoreactive insulin followed a similar pattern, but in diabetic subjects there was no significant difference between the three groups. We conclude that fructose or sorbitol, given as part of a meal, results in lower glucose levels in both normal and diabetic subjects, but that the latter is not related to a difference in insulin release.

The Effects of Sucrose, Fructose, and High-Fructose Corn Syrup Meals on Plasma Glucose and Insulin in Non-insulin-dependent Diabetic Subjects

We have previously shown that fructose and sorbitol given with a standard meal cause less increment in plasma glucose than sucrose and high fructose corn syrup (HFCS) in patients with NIDDM. However, there was no direct comparison of sucrose with HFCS. Sixteen men and one woman aged 54–67) with NIDDM were given either 35 g sucrose, 35 g fructose, or 43.75 g HFCS containing 35 g carbohydrate as part of a 400-calorie test meal. Blood samples were obtained at frequent intervals up to 3 h and were analyzed for glucose and insulin. As compared with a fructose meal, the mean increment in plasma glucose (ΔPG) after a sucrose meal was significantly higher at 45 min and after an HFCS meal it was significantly higher at 30 and 45 min, but sucrose and HFCS meals did not differ. When delta PGs were compared in nine patients with basal PG > 140 mg/dl and in eight patients with basal PG < 140 mg/dl, differences in ΔPG after sucrose and HFCS versus fructose meals became more significant but still did not differ from each other. The integrated total areas under the ΔPG curves after sucrose, HFCS, and fructose meals were not statistically different. However, the areas under the curves up to 90 min after sucrose and HFCS meals, which did not differ, were greater than the fructose meal. The mean delta IRI after sucrose meals was markedly elevated at 45, 60, and 75 min (P < 0.05) and after HFCS meals at 45 min as compared with fructose meals. There was no significant difference in the mean AIRI between sucrose and HFCS meals. This study shows that sucrose and HFCS cause greater increments of PG than fructose in patients with NIDDM, but do not differ from each other. Thus, even though HFCS is less expensive than fructose, its effect on plasma glucose and insulin is not different from that of sucrose, and we cannot confirm on a scientific basis a useful function for HFCS in diets for persons with diabetes. Also, diabetic patients with higher basal PG (i.e., > 140 mg/dl) show similar increase in PG whether they are given sucrose, HFCS, or fructose meals. Therefore, fructose has potential value only in patients with mild diabetes mellitus.

Enkephalins and Pituitary Hormone Release Modification of Responsiveness to LHRH

An intraperitoneal injection of leucine-enkephalin into rats stimulates gonadotropin and prolactin release. To elucidate the mechanism of this releasing property of leucine-enkephalin, rat hemipituitaries were incubated with either enkephalin alone or enkephalin in combination with OHRH. Enkephalin alone had no effect on LH or prolactin release in vitro but potentiated the LH response to LHRH. Neither leucine-enkephalin nor LHRH alone had an effect on GH release; however, when combined, a GH response to LHRH occurred. These results suggest that leucine-enkephalin can modify the pituitary responsiveness to certain hypothalamic releasing hormones by a direct pituitary action.

Rapid hydrogenation of unsaturated sterols and bile alcohols using microwaves

This paper describes an operationally simple, rapid hydrogenation of unsaturated sterols and bile alcohols in a domestic microwave oven. This has been achieved by the addition of catalytic amounts of Pd/C in methylene chloride/propylene glycol solvents in the presence of ammonium formate followed by microwave irradiation. It is suggested that this methodology will be helpful in the identification of saturated and unsaturated sterols with different side-chain structures in rare diseases: sitosterolemia, cerebrotendinous xanthomatosis (CTX), as well as atherosclerosis and diabetes mellitus. Sterols, such as cholesterol, campesterol, sitosterol, and bile alcohols with unsaturated side chains, were converted to their reduced congeners with high yield and purity.

Studies on N-nitroso bile acid amides in relation to their possible role in gastrointestinal cancer

Cancers of the gastrointestinal tract account for a large proportion of neoplastic diseases which afflict humans. The etiology of gastrointestinal cancer has been attributed in part to exogenous carcinogens, such as food substances and environmental pollutants. Recent hypotheses suggest that carcinogens may arise endogenously. Evidence suggests that some bile acids and their isomeric metabolites may be involved in the pathogenesis of colon cancer. However, the mechanism responsible for their cancer-promoting effect is not clear. We and others propose that one mechanism for the mitogenic effects of bile acids may be N-nitrosation of their glycine and taurine amides; human gastric aspirates do contain small quantities of N-nitroso compounds of other substrates. Many foods contain nitrites and nitrates, which can react with bile acid amides to form N-nitroso derivatives. Our recent studies demonstrated the potential for N-nitroso conjugate formation from ursodeoxycholic acid, a 7β-epimer of chenodeoxycholic acid used as a drug Actigall® to dissolve gallstones. The N-nitroso derivative of this compound, a direct-acting carcinogen, has a long half-life and, once nitrosated, is stable enough to survive passage through the gastrointestinal tract. We describe the synthesis of N-nitrosated derivatives of various bile acid conjugates and mechanisms of decomposition of (Z)- and (E)-bile acid diazoates. Studies of the effects of enzymes such as cholylglycine hydrolase on the N-nitroso bile acid conjugates and their reaction with DNA are also described. These studies may have important implications in the interplay of diet with endogenous substrates in the etiology of cancers of the stomach, liver, and colon.

Elevated prolactin levels in bronchogenic carcinoma

The frequency and significance of hyperprolactinemia was studied in 21 consecutive, untreated male patients with bronchogenic carcinoma. Seven patients (33%) were found to have elevated serum prolactin (hPRL) levels. No correlation was demonstrated between increased hPRL levels, tissue histology, or tumor burden. L‐dopa suppression and/or TRH stimulation tests were obtained in three untreated patients with hyperprolactinemia. The results of these tests were considered normal suggesting hypothalamic control. Cancer 44:676‐679, 1979.

Rapid hydrolysis of bile acid conjugates using microwaves: Retention of absolute stereochemistry in the hydrolysis of (25R) 3α,7α,12α-trihydroxy-5β-cholestan-26-oyltaurine

In recent years, defects of bile acid synthesis caused by disorders of peroxisome biogenesis have led to increased interest in C27 bile acids. In humans, while the majority of bile acids are C24 carboxylic acids, the presence of increased concentrations of C27 bile acids and their metabolites in hereditary diseases associated with peroxisomal dysfunction can serve as a useful marker for the intensity of the metabolic disorder. Our present studies describe an efficient method for the rapid hydrolysis of C27 and C24 bile acid conjugates using a commercial microwave oven. The advantages of this method include freedom from racemization, minimal activation, mild reaction conditions, and the highly stereocontrolled nature of the reaction, thus allowing for free bile acid recovery in high yield. For example, when (25R) 3α,7α,12α-trihydroxy-5β-cholestan-26-oyl taurine, a major compound present in the bile of Alligator mississippiensis, was deconjugated with 4% NaOH/diethylene glycol or 1 M LiOH/propylene glycol in the microwave oven for 4–6 min, 3α,7α,12α-trihydroxy-5β-cholestan-26-oic acid (THCA) was obtained in 81% yield with retention of configuration at C-25. It is suggested that present studies will be helpful in delineating the absolute stereochemistry of 3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA oxidase, the peroxisomal enzyme that catalyzes the first step in the oxidation of THCA.

The starved kidney: A defect in renal concentrating ability

The renal tubular responsiveness to antidiuretic hormone was assessed in seven obese patients during starvation and feeding by an overnight dehydration test followed by exogenous vasopressin. All seven subjects showed a mean reduction of one-third in their maximum urinary osmolality on day 4 of starvation. Thes- data show that the renal tubule is partially insensitive to antidiuretic hormone at a time when it is also insensitive to mineralocorticoids.?Author

7β-hydroxy bile alcohols: Facile synthesis and 2D 1H NMR studies of 5β-cholestane-3α,7β,12α,25-tetrol ☆

Abstract A rapid and easily performed procedure for the synthesis of 5β-cholestane-3α,7β,12α,25-tetrol by means of an efficient homologation sequence of the intermediate, 3α,7β,12α-triformyloxy-24-oxo-25-diazo-25-homo-5β-cholane is described. The reaction sequence involved treating the intermediate, α-diazoketone in methanol with 3% AgNO3 or Ag2O, anhydrous Na2CO3, Na 2 S 2 O 3 H 2 O resulting in the formation of homoursocholic acid in high yield. Esterification of the homoursocholic acid in methanol containing a catalytic amount of methanesulfonic acid under microwave irradiation conditions gave methyl homourscholate. The subsequent treatment of methyl homoursocholate with methyl magnesium iodide provided 5β-cholestane-3α,7β,12α,25-tetrol in 88% yield. The products and synthetic intermediates prepared in these studies were fully characterized by the results of 1D and 2D NMR, and high-resolution mass spectral studies. These studies will help in further investigation of the defect of cholic acid biosynthesis in patients with cerebrotendinous xanthomatosis (CTX) as well as other inborn errors of bile acid metabolism.

Plasma Glucose and Insulin After Fructose an High-Fructose Corn Syrup Meals in Subjects with Non-insulin-dependent Diabetes Mellitus

The impact on plasma glucose of 35 g of fructose or an equicaloric amount (43.75 g) of high-fructose corn syrup (HFCS) (as part of a 400-calorie meal) was measured in six patients with non-insulin-dependent diabetes mellitus (NIDDM). Blood samples were collected periodically at all points for all patients for 3 h for plasma glucose (PG) and insulin (IRI) determinations. The mean peak PG increment was higher after the HFCS meal (66.5 mg/dl) than after the fructose meals (45.5 mg/dl). When increase in the mean plasma glucose concentration (Δ PG) after the fructose meals were compared with the Δ PG after the HFCS meals, there was statistical significance at 15 min (P < 0.02) and 30 min (P < 0.05). The total areas under the 3-h curves of mean Δ PG showed a highly significant (P < 0.001) difference between the fructose meal (5601 planimetry U) compared with the HFCS meal (8023 planimetry U). Mean changes in IRI after meals with either sweetener were comparable. These findings suggest that fructose is superior to HFCS as a sweetening agent in patients with NIDDM.