A diabetogenic polypeptide from hog and sheep adenohypophysis similar to that found in lipoatrophic diabetes

Louis, Lawrence H.; Conn, Jerome W.

doi:10.1016/0026-0495(68)90038-3

Cited by 21 publications

(8 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A hypothalamic disturbance is considered pathogenetic in lipoatrophic diabetes, in both the congenital and acquired forms (1,6,22,24,26). Via abnormal neurohumoral signals a loss of fat in the subcutis and internal depots is induced concomitant with insulin resistance (1,21,24,29). How these signals act in detail is not known, but in both animal experiments and clinical studies, urinary peptides have been found with adipo- kinetic, diabetogenic and anti-insulin properties (7,20,21).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pancreatic B‐cell Function and Abnormal Urinary Peptides in a Boy With Lipoatrophic Diabetes and Stenosis of the Aqueduct of Sylvius

et al. 1980

View full text Add to dashboard Cite

A boy with the classical clinical manifestations of acquired lipoatrophic diabetes has been studied for 5 years from the onset of diabetes at age 13. At the age of 15 a ventriculo-cisternal shunt operation was performed because of stenosis of the aqueduct of Sylvius, followed by a dramatic improvement in his diabetic state with a decrease of the 24 hr insulin requirement from 130 to 32 units. After 12 months there was a relapse with increased insulin requirement up to the preoperative level. Pimozide treatment was given for 7 months with no effect on the metabolic derangements. Extremely high basal levels of serum C-peptide and pro-insulin were found throughout the period of observation. A further increase occurred after i.v. arginine infusion tests, indicating hyperfunctioning B-cells. Repeated screenings of peptides in the urine by sephadex chromatography revealed pathological patterns similar to those observed in patients with other hypothalamic disorders, but different from that found in the urine of patients with congenital generalized lipodystrophy. Injection into mice of peptides extracted from the preoperative urine produced an acute hyperglycemia. The mechanisms behind this hypothalamic syndrome are unknown, but it is postulated that the abnormal urinary polypeptides originate from disorganized hypothalamic centres and that these peptides may be responsible for the disturbed carbohydrate and lipid metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The condition is associated with hypothalamic dysfunction. It is thought that both abnormal humoral and neural stimuli may induce insulin resistance and loss of fat depots (1,6,7,20,21,22,24,26,29).…”

Section: Abstract: C-peptide Lipoatrophic Diabetes Urinary Polypepmentioning

confidence: 99%

Pancreatic B‐cell Function and Abnormal Urinary Peptides in a Boy With Lipoatrophic Diabetes and Stenosis of the Aqueduct of Sylvius

et al. 1980

View full text Add to dashboard Cite

show abstract

“…The effects of insulin and of the diabetogenic peptide on glycogen synthase activation (Table 2) were then evaluated on 4 and 5. 0.04 jug/ml of insulin = 1 mU/ml; 0.2 Ag/ml of insulin = 5 mU/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Evidence also suggests that this peptide is not adrenocorticotrophic hormone (3) or prolactin (4). Therefore, the suggestion has been made that this is a novel pituitary peptide (7).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Anti-Insulin Actions of a Bovine Pituitary Diabetogenic Peptide on Glycogen Synthesis

Miller¹,

Larner²

1972

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The site(s) of action of a bovine pituitary diabetogenic peptide that produces hyperglycemia and hyperinsulinemia in vivo (dogs or humans) was investigated in vitro. When rat diaphragms were incubated with the peptide in the presence of insulin, the peptide depressed insulin-mediated (a) glucose uptake, (b) glycogen synthesis, and (c) glycogen synthase activation (conversion of D to I form). Incubation with the peptide alone resulted in small increases in (a), (b), and (c). Insulin-mediated glycogen synthase kinase inactivation was inhibited when both insulin and peptide were present (d), whereas glycogen synthase kinase activity was lowered by the peptide alone. High doses of insulin completely reversed inhibitory effects of the peptide on glycogen synthesis. Therefore, the hyperglycemic and anti-insulin properties of this peptide in vivo can possibly be explained by the partial blocking action of the peptide on insulin-mediated glucose uptake and glycogenesis.In 1963, Louis et al.(1) first reported the isolation of a polypeptide exhibiting diabetogenic and anti-insulin properties from urine of human lipoatrophic diabetics. This peptide was not found in the urine of normal subjects. A similar peptide was subsequently isolated from urine of proteinuric diabetic patients without lipoatrophy (2), as well as from adenohypophyses of beef (3), sheep, pigs (4), and humans (5). All peptides produce hyperglycemia and resistance to exogenous insulin when injected into dogs and humans. After purification to homogeneity, all exhibit similar physicochemical and biological properties (5).The evidence that the pituitary peptide is not growth hormone or a fragment is: first, that it has no growth-promoting activity (6); second, no fragment of growth hormone with diabetogenic activity was isolated when growth hormone was subjected to the same isolation and purification procedures as the peptide (7); and third, there was little or no immunological crossreactivity between growth hormone antiserum and the peptide (5, 8). Evidence also suggests that this peptide is not adrenocorticotrophic hormone (3) or prolactin (4). Therefore, the suggestion has been made that this is a novel pituitary peptide (7).Since the biological effects of the peptide in vivo suggested an action antagonistic to insulin, we decided to examine this question directly in vitro. We have investigated the mechanism of action in terms of the well established stimulation by insulin of glucose uptake, glycogen synthesis, and the two enzyme perturbations that regulate the latter biochemical action. In the present paper we demonstrate that in addition to blocking each of these four actions of insulin in isolated rat diaphragm, the peptide alone acts as a weak positive effector 2774 on these same four parameters, suggesting that it may act very early in the sequence of actions initiated by insulin. METHODS AND MATERIALSMale Wistar rats (140-180 g) were decapitated and their diaphragms were dissected either with or without the rib cage. The diaphragms were place...

show abstract

Klinik des Diabetes mellitus

Jahnke¹

1975

Diabetes Mellitus · A

View full text Add to dashboard Cite

A diabetogenic polypeptide from hog and sheep adenohypophysis similar to that found in lipoatrophic diabetes

Cited by 21 publications

References 4 publications

Pancreatic B‐cell Function and Abnormal Urinary Peptides in a Boy With Lipoatrophic Diabetes and Stenosis of the Aqueduct of Sylvius

Pancreatic B‐cell Function and Abnormal Urinary Peptides in a Boy With Lipoatrophic Diabetes and Stenosis of the Aqueduct of Sylvius

Anti-Insulin Actions of a Bovine Pituitary Diabetogenic Peptide on Glycogen Synthesis

Klinik des Diabetes mellitus

Contact Info

Product

Resources

About