Utrastructural and morphometric studies of delta cells in pancreatic islets from C57BL/Ks diabetes mice

Leiter, Edward H.; Gapp, David A.; Eppig, John J.; Coleman, D L

doi:10.1007/bf01235886

Cited by 48 publications

(33 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This might lead to overestimation of β-cell contribution to the total ZRL1 fluorescence in live islets. However, δ-cells comprise less than 10% of total pancreatic islet content (Leiter et al, 1979). In agreement with a minor contribution of δ-cells, the ratio of the α-cell to β-cell mass in live islets calculated based on FQA is not significantly different from that obtained by IHC from pancreas slices isolated from mice with the same age in multiple experimental trials ( Figs 3D and 6F).…”

Section: Discussionsupporting

confidence: 79%

An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells

Wang

Han

Zhu

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Imbalanced glucagon and insulin release leads to the onset of type 2 diabetes. To pinpoint the underlying primary driving force, here we have developed a fast, non-biased optical method to measure ratios of pancreatic α-and β-cell mass and function simultaneously. We firstly label both primary α-and β-cells with the red fluorescent probe ZinRhodaLactam-1 (ZRL1), and then highlight α-cells by selectively quenching the ZRL1 signal from β-cells. Based on the signals before and after quenching, we calculate the ratio of the α-cell to β-cell mass within live islets, which we found matched the results from immunohistochemistry. From the same islets, glucagon and insulin release capability can be concomitantly measured. Thus, we were able to measure the ratio of α-cell to β-cell mass and their function in wild-type and diabetic Lepr db /Lepr db (denoted db/db) mice at different ages. We find that the initial glucose intolerance that appears in 10-week-old db/db mice is associated with further expansion of α-cell mass prior to deterioration in functional β-cell mass. Our method is extendable to studies of islet mass and function in other type 2 diabetes animal models, which shall benefit mechanistic studies of imbalanced hormone secretion during type 2 diabetes progression.

show abstract

Section: Discussionsupporting

confidence: 79%

An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells

Wang

Han

Zhu

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…The histological studies of Petkov et al (34) showed that islet damage in diabetic P. obesus is similar to that found in human diabetes, BB Wistar rats, and C57BL/KS mice (11,23,42). We have found that the mitochondrial potentiometric dye Rh123 appears to be an excellent tool for visualizing cell damage in intact islets, as it is highly permeable and specific to mitochondria.…”

Section: Discussionsupporting

confidence: 72%

Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabeticPsammomys obesus

Katzman¹,

Messerli²,

Barry³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

The cells within the intact islet of Langerhans function as a metabolic syncytium, secreting insulin in a coordinated and oscillatory manner in response to external fuel. With increased glucose, the oscillatory amplitude is enhanced, leading to the hypothesis that cells within the islet are secreting with greater synchronization. Consequently, non-insulin-dependent diabetes mellitus (NIDDM; type 2 diabetes)-induced irregularities in insulin secretion oscillations may be attributed to decreased intercellular coordination. The purpose of the present study was to determine whether the degree of metabolic coordination within the intact islet was enhanced by increased glucose and compromised by NIDDM. Experiments were performed with isolated islets from normal and diabetic Psammomys obesus. Using confocal microscopy and the mitochondrial potentiometric dye rhodamine 123, we measured mitochondrial membrane potential oscillations in individual cells within intact islets. When mitochondrial membrane potential was averaged from all the cells in a single islet, the resultant waveform demonstrated clear sinusoidal oscillations. Cells within islets were heterogeneous in terms of cellular synchronicity (similarity in phase and period), sinusoidal regularity, and frequency of oscillation. Cells within normal islets oscillated with greater synchronicity compared with cells within diabetic islets. The range of oscillatory frequencies was unchanged by glucose or diabetes. Cells within diabetic (but not normal) islets increased oscillatory regularity in response to glucose. These data support the hypothesis that glucose enhances metabolic coupling in normal islets and that the dampening of oscillatory insulin secretion in NIDDM may result from disrupted metabolic coupling.

show abstract

“…On the other hand, there is an increase in volume density of glucagon, somatostatin and pancreatic polypeptide secreting cells with an alteration in their peripheral localization (Baetans, Stefan, Ravazzola, Malaisse-Lagae, Coleman & Orci, 1978). Leiter, Gapp, Eppig & Coleman (1979) Assays have demonstrated that these mutants are hyperglucagonaemic (Stearns & Benzo, 1978) and that pancreatic somatostatin is elevated (Makino, Matsushima, Kanatsuka, Yamamoto, Kumagai & Nishimura, 1979). Very recently Berelowitz & Frohman (1983) have reported on immunoreactive neurotensin in the db/db pancreas.…”

Section: Islets Of Langerhans Functionmentioning

confidence: 99%

Mouse Mutants as Models in Endocrine Research

Charlton

1984

Exp Physiol

View full text Add to dashboard Cite

Although Shire (1979) has listed some forty‐eight mouse mutants of interest to the endocrinologist, this short review has concentrated upon eleven mutations which have resulted in a significant number of scientific publications over the last 4 or 5 years. The selection of references has had to be limited, but it should be possible easily to expand the list given in this review. Although the proximate cause of none of the eleven mutations has been identified with certainty, the abnormalities of function have included hormone deficiencies and receptor and post‐receptor malfunctions. It is perhaps a reflexion on our society in the 1980s, that the bulk of research has concentrated on the obese mouse. However, we still do not know the initial cause of this syndrome. The major disadvantage of the mouse to the hormone assayist lies in the small blood volume and the extreme difficulty in taking serial blood samples over a short period of time. With increased sophistication of assay techniques this may prove less daunting, but is an area where a review of the literature reveals discrepancies between laboratories, and even between data generated by the same laboratory at different times. With regard to the hormone content of endocrine tissues, the way forward for peptide‐secreting glands may be in the measurement of mRNA levels for particular hormones. Certainly the methods of recombinant‐DNA technology will yield positive information upon the aetiology and expression of some of the syndromes considered above. Organ transplantation is an area in which mutant mice have proved useful, for example gonadal, pituitary and pancreatic tissue transplantation. The grafting of neural tissue in the hpg mouse has added a further dimension to this field of research. The great infrastructure of genetical research in mice has enabled us to breed mutant genes onto different genetic backgrounds. This area of research is one which deserves to expand. The techniues of in vitro fertilization, chimera formation and embryo transfer have been used, in part, in studies on mouse mutants, and should provide technical means for further investigating gene expression. The family of dwarf mutants are ideally suited for research into the expression of genes micro‐injected into the fertilized egg (see Charlton & Cox, 1983). As new hormones are isolated and become available for study these mouse mutants may well be useful in delineating physiological functions for natural and pharmacological products. Again, the dwarf mutants would seem ideally suited for research into the synthesis and action of GRF. Mouse mutants have proved of use to biochemists and embryologists and provide fertile ground for endocrine investigations ranging from molecular genetics to membrane biophysics.

show abstract

Utrastructural and morphometric studies of delta cells in pancreatic islets from C57BL/Ks diabetes mice

Cited by 48 publications

References 30 publications

An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells

An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells

Mitochondrial metabolism reveals a functional architecture in intact islets of Langerhans from normal and diabeticPsammomys obesus

Mouse Mutants as Models in Endocrine Research

Contact Info

Product

Resources

About