The Ability of Pancreatic Polypeptides (APP and BPP) to Return to Normal the Hyperglycaemia, Hyperinsulinaemia and Weight Gain of New Zealand Obese Mice

Gates, R J; Lazarus, N R

doi:10.1159/000178800

Cited by 72 publications

(14 citation statements)

References 9 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although earlier studies suggested a possible defect in the development of pancreatic peptide-positive (PP) cells in the islets of NZO/Wehi mice (Gates and Lazarus, 1977;Gates et al, 1972Gates et al, , 1974, we observed numerous granulated PP-cells, as well as glucagoncontaining alpha cells. Although less numerous, somatostain containing delta cells were also demonstrable by immunochemical staining (Fig.…”

Section: Junger Et Alcontrasting

confidence: 92%

“…An alloimmune rejection would be anticipated across this major histocompatibility barrier. Further, the observation that NZO islets are rich in PP cells refutes an earlier suggestion that there is a genetic lack of PP, and further makes it unlikely that PP from other islet sources would be curative, as reported previously (Gates and Lazarus, 1977).…”

Section: Junger Et Alsupporting

confidence: 83%

See 1 more Smart Citation

The Diabetes-Prone NZO/Hl Strain. II. Pancreatic Immunopathology

Junger¹,

Herberg²,

Jeruschke³

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:We report the first combined light and electron microscopic analysis of the pancreas during the development of type 2 diabetes in the New Zealand Obese (NZO) mouse. As in most other polygenic rodent models of type 2 diabetes, hyperglycemia associated with beta cell destruction is male sex-limited. Increasing degrees of hyperinsulinemia and transition to diabetes were clearly reflected by the islet volume fraction, by the beta cell granulation state, and by ultrastructural changes, primarily of the endoplasmic reticulum. One of the unusual histopathologic features of NZO mice of both sexes was the presence of B-lymphocyte enriched leukocytic aggregates in the pancreas. Immunocytochemical analysis of the pancreas of 52-week-old diabetic males indicated enrichment for CD19 ϩ B lymphocytes. Staining of adjacent sections for CD3 and CD5 indicated CD5 coexpression on some of the CD19 ϩ cells, suggesting the presence of the B1-B subset associated with generation of natural autoantibodies in other autoimmune-prone New Zealand mouse strains. In addition, plasma cells in peri-insular leukocytic infiltrates were identified by electron microscopy. Hence, although autoimmunity has previously proven to be a secondary manifestation of beta cell destruction in most rodent models of type 2 diabetes, the present observations suggest that B lymphocyte function, in association with male gender, may contribute to the development of insulin resistance and chronic hyperglycemia in the NZO model. (Lab Invest 2002, 82:843-853).

show abstract

Section: Junger Et Alcontrasting

confidence: 92%

Section: Junger Et Alsupporting

confidence: 83%

The Diabetes-Prone NZO/Hl Strain. II. Pancreatic Immunopathology

Junger¹,

Herberg²,

Jeruschke³

et al. 2002

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Although the half-life is of the order of 5 min the levels remain increased for several hours, indicating a continuous release (8). Injections ofbovine PP (bPP) decrease food intake and body weight in the hyperglycemic ob/ob mouse (9), and injections of either the bovine or avian PP (aPP) cause New Zealand obese mice to revert to normal (10). Although these observations indicate that PP may act as a satiety factor, the peptide appears to have other physiological effects in addition, including increased gut motility and "gastrin-like" actions (11,12).…”

mentioning

confidence: 99%

X-ray analysis (1. 4-Å resolution) of avian pancreatic polypeptide: Small globular protein hormone

Blundell

Pitts

Tickle

et al. 1981

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

269

156

View full text Add to dashboard Cite

The crystal structure of avian pancreatic polypeptide (aPP), a 36-residue polypeptide with some hormonal properties, has been determined by using single isomorphous replacement and anomalous scattering to 2.1-A resolution. The phases were extended to 1.4-A resolution by using a modified tangent formula. The molecule contains two regions ofsecondary structurean extended polyproline-like helix (residues 1-8) and an a-helix (residues 14-31) -that run roughly antiparallel. The packing together of nonpolar groups from these regions gives the molecule a hydrophobic core in spite of its small size. The aPP molecules form a symmetrical dimer in the crystal stabilized principally by interlocking of nonpolar groups from the a-helices. The aPP dimers are crosslinked by coordination ofZn"+; three aPP molecules contribute ligands to each zinc. The coordination geometry is a distorted trigonal bipyramid. The properties of the aPP molecule in solution are consistent with expectations based on the crystal structure. The aPP molecule has several general features in common with the pancreatic hormones insulin and glucagon. All three hormones have complex mechanisms for self-association. Like insulin, aPP seems to have a stable monomeric structure but its biological activity seems to depend on the more flexible COOH-terminal region analogous to the flexible NH2-terminal region of glucagon.Pancreatic polypeptide (PP) is a 36-amino acid peptide found in the endocrine pancreas (1, 2). There is close sequence homology among the mammalian peptides although mammalian and avian PPs differ at about 20 positions (Fig. 1). All sequences have an amidated COOH terminus, a feature known to occur in other polypeptide hormones such as gastrin, secretin, and oxytocin (3). There is now evidence that PP is synthesized as a larger precursor, in the same way as other pancreatic polypeptide hormones (4).The ultrastructural appearance ofthe PP-producing cells also strongly argues for an endocrine function for this peptide. PP is located in membrane-enclosed granules (5) like those of the alpha and beta pancreatic cells in which glucagon and insulin are synthesized. The PP cells are located on the periphery of the islets at the head of the pancreas, to the exclusion of glucagon cells which occur at the periphery of the islets of the tail end (6). In certain fishes such as the teleost Cottus scorpius, which has two principal islets, the pyloric region has mainly PP cells and the splenic contains no PP cells (7).PP is released into the circulation partly as a result of vagal cholinergic stimulation after feeding or in response to hypoglycemia. Although the half-life is of the order of 5 min the levels remain increased for several hours, indicating a continuous release (8). Injections ofbovine PP (bPP) decrease food intake and body weight in the hyperglycemic ob/ob mouse (9), and injections of either the bovine or avian PP (aPP) cause New Zealand obese mice to revert to normal (10). Although these observations indicate that PP may act as a satiety...

show abstract

“…injection reduces food intake and weight gain in ob/ob mice [160]. In New Zealand obese mice, similar treatment reduces hyperglycaemia, hyperinsulinaemia and weight gain [162]. More recent studies have shown that mice with selective transgenic overexpression of PP in pancreatic islets, resulting in a 20-fold increase in plasma PP concentration, are lean and hypophagic in comparison with controls [163].…”

Section: Pancreatic Polypeptidementioning

confidence: 99%

Obesity treatment: novel peripheral targets

Field¹,

Chaudhri²,

Bloom³

2009

Brit J Clinical Pharma

View full text Add to dashboard Cite

Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short-and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies.

show abstract

The Ability of Pancreatic Polypeptides (APP and BPP) to Return to Normal the Hyperglycaemia, Hyperinsulinaemia and Weight Gain of New Zealand Obese Mice

Cited by 72 publications

References 9 publications

The Diabetes-Prone NZO/Hl Strain. II. Pancreatic Immunopathology

The Diabetes-Prone NZO/Hl Strain. II. Pancreatic Immunopathology

X-ray analysis (1. 4-Å resolution) of avian pancreatic polypeptide: Small globular protein hormone

Obesity treatment: novel peripheral targets

Contact Info

Product

Resources

About