Gene F. Tutwiler

Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid (TDGA) on glucose and fatty acid oxidation in isolated rat soleus muscle

1. The effect of 2-tetradecylglycidic acid (TDGA), a potent, specific inhibitor of long-chain fatty acid oxidation, on fatty acid and glucose oxidation by isolated rat soleus muscle was studied. 2. TDGA inhibited [1-14C]palmitate oxidation by soleus muscle in a concentration-dependent manner. 3. TDGA inhibited the activity of soleus muscle mitochondrial carnitine palmitoyltransferase A (CPT-A). 4. Added palmitate (0.5 mM) significantly inhibited D-[U-14C]glucose oxidation and, under conditions where TDGA inhibited palmitate oxidation, the oxidation of D-[U-14C]glucose by isolated soleus muscle was significantly stimulated. 5. TDGA stimulation of glucose oxidation was reversed by octanoate, a medium-chain fatty acid whose oxidation is not inhibited by TDGA. 6. When nondiabetic rats were treated with TDGA (10 mg/kg p.o./day x 3 days), fasting plasma glucose was significantly lowered and the ability of isolated contralateral soleus muscles to oxidize palmitate was inhibited while glucose oxidation was significantly stimulated.

Glycostatic effect of a diabetogenic non-growth-promoting pituitary polypeptide☆

Abstract 1. 1. Treatment with a mg. of a non-growth-promoting bovine diabetogenic peptide or growth hormone in two divided doses, one at the beginning and one 7–9 hours later, to hypophysectomized rats during a 24-hour fast maintained their muscle glycogen at a normal level. 2. 2. Administration of bovine serum albumin or saline was accompanied by a sharp decrease of muscle glycogen. 3. 3. The minimum dose of highly purified bovine diabetogenic peptide which is capable of maintaining muscle glycogen at normal levels was found to be 0.2–0.3 mg. in 135–150-g. rats. 4. 4. Diabetogenic peptide maintains muscle glycogen in fasted hypophysectomizedadrenalectomized rats. 5. 5. Diabetogenic peptide does not promote growth as measured by the tibia test.

Further observations on a diabetogenic protein from bovine adenohypophysis

Abstract 1. 1. The bovine pituitary diabetogenic protein described by Louis, Conn & Minick ( 1966), which is similar to that found in the urine of proteinuric and lipoatrophic diabetics, has been isolated and purified by a slightly modified procedure. 2. 2. Extensive studies in dogs confirm that this protein causes hyperglycaemia, glycosuria and insulin resistance. 3. 3. In addition, this material induces polyuria, polydypsia, elevation in free fatty acids but not cholesterol and triglycerides, lowered plasma urea nitrogen without change in urine urea nitrogen and no ketonuria in dogs. 4. 4. This protein had little growth-promoting activity in hypophysectomized rats.

Effect of a diabetogeic factor from bovine adenohypophysis on dog serum nefa levels

Abstract 1. 1. Fasted dog serum non-esterified fatty acid (NEFA) levels were elevated 10 and 34 hours after administration of a diabetogenic protein (BDF) isolated from bovine adenohypophysis. 2. 2. The fasting serum NEFA were elevated in spite of the presence of normal or high glucose and insulin levels. 3. 3. After oral glucose administration to BDF-treated animals, a fall of serum NEFA paralleled inversely the increasing levels of blood glucose and serum insulin. 4. 4. These data are discussed with respect to the insulin-antagonistic action of BDF. Even though the plasma NEFA fell in response to glucose in BDF-treated animals, the NEFA during the entire 3-hour glucose-tolerance test were always significantly higher than the levels observed in the control tests. 5. 5. Since BDF is similar to the diabetogenic protein isolated from the urine of patients with lipoatrophic diabetes, its lipid-mobilizing action might help to explain the lipoatrophy, hyperlipaemia, diabetes mellitus, and insulin resistance seen in lipoatrophic diabetic patients.

Immunological characterization of a diabetogenic protein from bovine adenohypophysis

l. A diabetogenic protein isolated from bovine adenohypophysis which had previously been demonstrated to cause fasting hyperglycemia and decreased glucose tolerance in dogs and man is highly antigenic when injected into rabbits. 2. Immunoelectrophoresis and gel double diffusion studies did not provide evidence of multiple antibodies or antigens in the bovine diabetogenic protein: anti-bovine diabetogenic system. 3. Results of agar diffusion studies in which anti-bovine diabetogenic protein serum did not visibly react with homologous bovine serum proteins, serum albumin, ACTH or prolactin lend supporting evidence for the homogeneity of the reaction between bovine diabetogenic protein and its antiserum. 4. A comparative immunological study of diabetogenic proteins from various species was performed using agar double diffusion studies

Hypoglycaemic effect of a bovine diabetogenic protein in rats and mice

Abstract 1. 1. A diabetogenic protein isolated from bovine adenohypophysis, which had previously been demonstrated to cause fasting hyperglycaemia and decreased glucose tolerance in dogs and man, induces fasting hypoglycaemia and increased glucose tolerance 4–6 hours after intraperitoneal injection into rats. 2. 2. The diabetogenic protein elevated rat fasting free fatty acids, but did not alter the cholesterol and blood urea nitrogen (BUN) levels. 3. 3. The diabetogenic protein induces fasting hypoglycaemia in mice. 4. 4. The hypoglycaemia induced by the diabetogenic protein is not the result of contamination by growth hormone.

Influence of bovine diabetogenic peptide, growth hormone, and prolactin on tissue glycogen, liver fat, and liver water of fasting rats

Abstract 1. 1. Bovine diabetogenic peptide, growth hormone, and prolactin were compared with respect to their effects on tissue glycogen, liver fat, and liver water in fasting rats. 2. 2. Bovine diabetogenic peptide increases liver size, liver glycogen, liver water, and total liver lipids. 3. 3. Bovine diabetogenic peptide, in contrast to growth hormone and prolactin, does not increase muscle glycogen levels.

Immunological cross-reaction of bovine growth hormone (NIH-GH-B8) with the antiserum to the bovine diabetogenic protein☆

Abstract 1. 1. The immunological cross-reaction of bovine growth hormone (BGH, NIH-GH-D8) with the antiserum to the bovine diabetogenic protein (BDP) has been determined to be the result of contamination of the BGH preparation with a highly anionic protein. 2. 2. This highly anionic protein is probably BDP.

Diabetogenic protein from the urine of proteinuric diabetic patients.

Abstract 1. 1. A protein fraction (Fraction P 1 ) which produces a diabetogenic effect in dogs and a lipolytic effect in vivo and in vitro has been isolated from the urine of proteinuric diabetic patients. 2. 2. Fraction P 1 was found to be heterogeneous and was difficult to purify because of extensive aggregation. 3. 3. Some separation was achieved using Sephadex G-100 chromatography in the presence of 6 M urea, however, both high (void volume) and low molecular weight fractions (molecular weight—20,000–22,000) produced diabetogenic effects. 4. 4. This protein(s) was shown not to be growth hormone or prolactin.